Publications

Sengupta Laboratory at

Harvard Medical School and MIT

Recent Selected Publications

Sengupta S. Cancer nanomedicine: lessons for immuno-oncology. Trends in Cancer. 2017 Aug;3(8):551-560

This review discusses the two key parameters that defined clinical success in the case of cancer nanomedicines: (i) physicochemical design principles, and (ii) clinical trial design, which are frequently overlooked in most analyses of the state of the field. Learning from the design principles that defined success for the clinically-used cancer nanomedicines can enable the design of next-generation nanomedicines that can address some of the emerging challenges in cancer immunotherapy, for example (i) enabling combinations of molecularly targeted therapies with immunotherapies that are pharmacologically incompatible; (ii) early monitoring of efficacy of immunotherapies; and (iii) personalizing an immune response to a patient's tumor.

Kulkarni A, et al. A designer self-assembled supramolecule amplifies macrophage immune responses against aggressive cancer. Nature Biomed. Eng. 2018; 2: 589-599

Effectively activating macrophages that can ‘eat’ cancer cells is challenging. In particular, cancer cells secrete macrophage colony stimulating factor (MCSF), which polarizes tumour-associated macrophages from an antitumour M1 phenotype to a pro-tumorigenic M2 phenotype. Also, cancer cells can express CD47, a ‘don’t eat me’ signal that ligates with the signal regulatory protein alpha (SIRPα) receptor on macrophages to prevent phagocytosis. Here, we show that a supramolecular assembly consisting of amphiphiles inhibiting the colony stimulating factor 1 receptor (CSF-1R) and displaying SIRPα-blocking antibodies with a drug-to-antibody ratio of 17,000 can disable both mechanisms. The supramolecule homes onto SIRPα on macrophages, blocking the CD47–SIRPα signalling axis while sustainedly inhibiting CSF-1R. The supramolecule enhances M2-to-M1 repolarization within the tumour microenvironment, and significantly improves antitumour and antimetastatic efficacies in two aggressive animal models of melanoma and breast cancer.

Gupta N, et al. Development of a facile antibody-drug conjugate platform for increased stability and homogeneity. Chemical Sciences. 2017; 8: 2387-2395

We report, for the first time, an ADC platform technology using a platinum(ii)-based linker that can re-bridge the inter-chain cysteines in the antibody, post-reduction. The strong platinum-sulfur interaction improves the stability of the ADC when compared with a standard maleimide-linked ADC thereby reducing the linker-drug exchange with albumin significantly. Moreover, due to the precise conserved locations of cysteines, both homogeneity and site-specificity are simultaneously achieved. Additionally, we demonstrate that our ADCs exhibit increased anticancer efficacy in vitro and in vivo.

Kulkarni AA, et al. “Rationally designed 2-in-1 nanoparticles can overcome adaptive resistance in cancer”, ACS Nano. 2016; 10: 5823-5824

Should a combination of two drugs be delivered from a single nanoparticle or should they be delivered in two different nanoparticles for maximal efficacy? We explored these questions in the context of adaptive resistance, which emerges as a phenotypic response of cancer cells to chemotherapy. We studied the phenotypic dynamics of breast cancer cells under cytotoxic chemotherapeutic stress and analyzed the data using a phenomenological mathematical model. We demonstrate that cancer cells can develop adaptive resistance by entering into a predetermined transitional trajectory that leads to phenocopies of inherently chemoresistant cancer cells. Disrupting this deterministic program requires a unique combination of inhibitors and cytotoxic agents. Using two such combinations, we demonstrate that a 2-in-1 nanomedicine can induce greater antitumor efficacy by ensuring that the origins of adaptive resistance are terminated by deterministic spatially constrained delivery of both drugs to the target cells. In contrast, a combination of free-form drugs or two nanoparticles, each carrying a single payload, is less effective, arising from a stochastic distribution to cells. These findings suggest that 2-in-1 nanomedicines could emerge as an important strategy for targeting adaptive resistance, resulting in increased antitumor efficacy.

Kulkarni AA, et al. “Combining immune checkpoint inhibitors and kinase-inhibiting supramolecular therapeutics for enhanced anti-cancer efficacy”, ACS Nano. 2016; 10: 9227–9242
Here we describe two case studies where nanoscale MEK- and PI3K-targeting supramolecular therapeutics were engineered using a quantum mechanical all-atomistic simulation-based approach. The combinations of nanoscale MEK- and PI3K-targeting supramolecular therapeutics with checkpoint PDL1 and PD1 inhibitors exert enhanced antitumor outcome in melanoma and breast cancers in vivo, respectively. Additionally, the temporal sequence of administration impacts the outcome. The combination of supramolecular therapeutics and immunotherapy could emerge as a paradigm shift in the treatment of cancer.

Kulkarni AA, et al. “Algorithm for designing nanoscale supramolecular therapeutics with increased anticancer efficacy”, ACS Nano. 2016; 10: 8154-68

In the chemical world, evolution is mirrored in the origin of nanoscale supramolecular structures from molecular subunits. However, the design of supramolecular nanostructures is hindered by a limited atomistic level understanding of interactions between building blocks. Here, we report the development of a computational algorithm, which we term Volvox after the first multicellular organism, that sequentially integrates quantum mechanical energy-state- and force-field-based models with large-scale all-atomistic explicit water molecular dynamics simulations to design stable nanoscale lipidic supramolecular structures. In one example, we demonstrate that Volvox enables the design of a nanoscale taxane supramolecular therapeutic. In another example, we demonstrate that Volvox can be extended to optimizing the ratio of excipients to form a stable nanoscale supramolecular therapeutic. The nanoscale taxane supramolecular therapeutic exerts greater antitumor efficacy than a clinically used taxane in vivo. Volvox can emerge as a powerful tool in the design of nanoscale supramolecular therapeutics for effective treatment of cancer.

Featured in a Perspective Article

Decuzzi P. Facilitating the Clinical Integration of Nanomedicines: The Roles of Theoretical and Computational Scientists, ACS Nano. 2016 10 (9), 8133-8138

Kulkarni AA, et al. “Reporter nanoparticle that monitors its anticancer efficacy in real time.”, Proc Natl Acad Sci U S A, 2016; 1: E2104-13
Currently, clinical readouts of anticancer efficacy rely on indirect or anatomic measurements, which occur over prolonged time scales postchemotherapy or postimmunotherapy and may not be concordant with the actual effect. Here we describe the biology-inspired engineering of a simple 2-in-1 reporter nanoparticle that not only delivers a cytotoxic or an immunotherapy payload to the tumor but also reports back on the efficacy in real time. The reporter nanoparticles are engineered from a novel two-staged stimuli-responsive polymeric material. Using chemotherapy-sensitive and chemotherapy-resistant tumors in vivo, we show that the reporter nanoparticles can provide a real-time noninvasive readout of tumor response to chemotherapy. The reporter nanoparticle can also monitor the efficacy of immune checkpoint inhibition in melanoma. The self-reporting capability, for the first time to our knowledge, captures an anticancer nanoparticle in action in vivo.

Editor’s Choice article on the above publication:
Kostic M. Seeing is believing. Cell Chemical Biology. 2016; 23: 428

Goldman A. et al. Temporally sequenced anticancer drugs overcome adaptive resistance by targeting a vulnerable chemotherapy-induced phenotypic transition. Nature Commun. 2015; 6: 6139Understanding the emerging models of adaptive resistance is key to overcoming cancer chemotherapy failure. Using human breast cancer explants, in vitro cell lines, mouse in vivo studies and mathematical modelling, here we show that exposure to a taxane induces phenotypic cell state transition towards a favoured transient CD44(Hi)CD24(Hi) chemotherapy-tolerant state. This state is associated with a clustering of CD44 and CD24 in membrane lipid rafts, leading to the activation of Src Family Kinase (SFK)/hemopoietic cell kinase (Hck) and suppression of apoptosis. The use of pharmacological inhibitors of SFK/Hck in combination with taxanes in a temporally constrained manner, where the kinase inhibitor is administered post taxane treatment, but not when co-administered, markedly sensitizes the chemotolerant cells to the chemotherapy. This approach of harnessing chemotherapy-induced phenotypic plasticity could emerge as a translational strategy for the management of cancer.

Majumder B, et al. Predicting clinical response to anticancer drugs using an ex vivo platform that captures tumour heterogeneity. Nature Commun. 2015; 6: 6169 Currently, clinical readouts of anticancer efficacy rely on indirect or anatomic measurements, which occur over prolonged time scales postchemotherapy or postimmunotherapy and may not be concordant with the actual effect. Here we describe the biology-inspired engineering of a simple 2-in-1 reporter nanoparticle that not only delivers a cytotoxic or an immunotherapy payload to the tumor but also reports back on the efficacy in real time. The reporter nanoparticles are engineered from a novel two-staged stimuli-responsive polymeric material. Using chemotherapy-sensitive and chemotherapy-resistant tumors in vivo, we show that the reporter nanoparticles can provide a real-time noninvasive readout of tumor response to chemotherapy. The reporter nanoparticle can also monitor the efficacy of immune checkpoint inhibition in melanoma. The self-reporting capability, for the first time to our knowledge, captures an anticancer nanoparticle in action in vivo.

Connor Y, et al. Physical nanoscale conduit-mediated communication between tumour cells and the endothelium modulates endothelial phenotype. Nature Commun. 2015; 6: 8671

Metastasis is a major cause of mortality and remains a hurdle in the search for a cure for cancer. Not much is known about metastatic cancer cells and endothelial cross-talk, which occurs at multiple stages during metastasis. Here we report a dynamic regulation of the endothelium by cancer cells through the formation of nanoscale intercellular membrane bridges, which act as physical conduits for transfer of microRNAs. The communication between the tumour cell and the endothelium upregulates markers associated with pathological endothelium, which is reversed by pharmacological inhibition of these nanoscale conduits. These results lead us to define the notion of 'metastatic hijack': cancer cell-induced transformation of healthy endothelium into pathological endothelium via horizontal communication through the nanoscale conduits. Pharmacological perturbation of these nanoscale membrane bridges decreases metastatic foci in vivo. Targeting these nanoscale membrane bridges may potentially emerge as a new therapeutic opportunity in the management of metastatic cancer.

Sengupta P, et al. A cholesterol-tethered platinum ii-based supramolecular nanoparticle increases antitumor efficacy and reduces nephrotoxicity. Proc. Natl. Acad. Sci. (USA), 2012; 109: 11294-9

Nanoscale drug delivery vehicles have been harnessed extensively as carriers for cancer chemotherapeutics. However, traditional pharmaceutical approaches for nanoformulation have been a challenge with molecules that exhibit incompatible physicochemical properties, such as platinum-based chemotherapeutics. Here we propose a paradigm based on rational design of active molecules that facilitate supramolecular assembly in the nanoscale dimension. Using cisplatin as a template, we describe the synthesis of a unique platinum (II) tethered to a cholesterol backbone via a unique monocarboxylato and O→Pt coordination environment that facilitates nanoparticle assembly. TThe nanoparticles exhibit significantly enhanced in vivo antitumor efficacy in murine 4T1 breast cancer and in K-Ras(LSL/+)/Pten(fl/fl) ovarian cancer models with decreased systemic- and nephro-toxicity. Our results indicate that integrating rational drug design and supramolecular nanochemistry can emerge as a powerful strategy for drug development.

Sengupta S, et al. Novel cancer therapy through temporal targeting of both tumor cells and neovasculature using a unique nanoscale delivery system. Nature 2005; 436: 568-72

Here we report the disease-driven engineering of a drug delivery system, a 'nanocell', which overcomes these barriers unique to solid tumours. The nanocell was the first layer by layer nanoparticle, comprising a nuclear nanoparticle within an extranuclear pegylated-lipid envelope, and is preferentially taken up by the tumour. The nanocell enables a temporal release of two drugs: the outer envelope first releases an anti-angiogenesis agent, causing a vascular shutdown; the inner nanoparticle, which is trapped inside the tumour, then releases a chemotherapy agent. This focal release within a tumour results in improved therapeutic index with reduced toxicity. The technology can be extended to additional agents, so as to target multiple signalling pathways or distinct tumour compartments, enabling the model of an 'integrative' approach in cancer therapy.

Publications

1. Gupta SK, Prakash J, Awor L, Joshi S, Velpandian T, Sengupta S. Anti-inflammatory activity of topical nimesulide gel in various experimental models. Inflamm. Res. 1996; 45: 590-592

2. Gupta SK, Velpandian T, Mathur P, Sengupta S. Comparative analgesic activity of nimesulide and diclofenac by intramuscular route: correlation with pharmacokinetic profile of nimesulide. Pharmacology 1998; 56: 137-143

3. Gupta SK, Velpandian T, Sengupta S, Mathur P, Sapra P. Influence of piperine on nimesulide induced antinociception. Phytother. Res. 1998;12: 266-269

4. Sengupta S, Velpandian T, Sapra P, Mathur P, Gupta S K. Comparative analgesic efficacy of nimesulide and diclofenac gels after topical application on the skin. Skin Pharmacol. Appl. Skin Physiol.1998;11: 273-278

5. Velpandian T, Mathur P, Sengupta S, Gupta S K. Preventive effect of chyavanprash against steroid induced cataract in the developing chick embryo. Phytother. Res. 1998; 12: 320-323

6. Sengupta S, Velpandian T, Kabir SR, Gupta S K. Analgesic efficacy and pharmacokinetics of topical nimesulide gel in healthy human volunteers: double-blind comparison with piroxicam, diclofenac and placebo. Eur J Clin Pharmacol 1998; 54: 541-547

7. Sengupta S, Tyagi P, Velpandian T, Gupta Y K, Kochupillai V, Gupta S K. Evaluation of the antitumour activity of liposomal formulations of etoposide against choriocarcinoma xenografts in balb/c nu/nu mice. Pharm. Pharmacol. Commun. 1999; 5: 595-598

8. Sengupta S, Sanyal M, Kochupillai V, Gupta S K. Expression of inducible and neuronal nitric oxide synthase in 20-methyl cholanthrene (20-mca) induced fibrosarcoma. Ind. J. Pharmacology 1999; 31: 315-318

9. Gupta SK, Bhardwaj RK, Tyagi P, Sengupta S, Velpandian T. Anti-inflammatory activity and pharmacokinetic profile of a new parenteral formulation of nimesulide. Pharmacological Research 1999; 39: 137-141

10. Sengupta S, Tyagi P, Velpandian T, Gupta Y K, Gupta S K. Etoposide encapsulated in positively charged liposomes: pharmacokinetic studies in mice and formulation stability studies. Pharmacological Research. 2000; 42: 459-464

11. Sengupta S, Tyagi P, Chandra S, Kochupillai V, Gupta S K. Encapsulation in cationic liposomes enhances antitumour efficacy and reduces the toxicity of etoposide, a topo-isomerase ii inhibitor. Pharmacology. 2001; 62: 163-71

12. Sengupta S, Sellers LA, Cindrova T, Skepper JN, Gherardi E, Sasisekheran R, Fan TP. Cyclooxygenase-2-selective non-steroidal anti-inflammatory drugs inhibit hepatocyte growth factor/scatter factor-induced angiogenesis. Cancer Res. 2003; 63: 8351-8359

13. Sengupta S, Seller LA, Li R, Zhao G, Gherardi E, Sasisekharan R, Fan TP. Targeting of mitogen activated protein kinases and phosphatidylinositol 3 kinase inhibits hepatocyte growth factor/scatter factor-induced angiogenesis. Circulation 2003; 107: 2955-2961

14. Sengupta S, Sellers LA, Matheson HB, Fan TP. Thymidine phosphorylase induces angiogenesis in vitro and in vivo: an evaluation of possible mechanisms. Br. J. Pharmacol. 2003; 139: 219-231

15. Sengupta S, Gherardi E, Sellers LA, Sasisekharan R, Fan TP. Hepatocyte growth factor/scatter factor can induce angiogenesis independent of vascular endothelial growth factor. Arterioscler. Thromb. Vasc. Biol. 2003; 23: 69-7

16. Qi Y, Zhao G, Liu D, Shriver Z, Sundaram M, Sengupta S, Venkataraman G, Langer R, Sasisekharan R. Delivery of therapeutic levels of heparin and low molecular weight heparin through a pulmonary route. Proc. Natl. Acad. Sci. (USA) 2004; 101: 9867-9872

17. Sengupta S, Kiziltepe T, Sasisekharan R. A dual color fluorescence imaging-based system for the dissection of the antiangiogenic and chemotherapeutic properties of molecules. FASEB J. 2004; doi:10.1096/fj.04-1934fje

18. Johnson NA, Sengupta S, Saidi SA, Lessan K, Charnock-Jones SD, Scott L, Stephens R, Freeman TC, Tom BDM, Harris M, Denyer G, Sundaram M, Sasisekharan R, Smith SK, Print CG. Endothelial cells preparing to die by apoptosis initiate a program of transcriptome and glycome regulation. FASEB J. 2004; 18: 188-190

19. Sengupta S, Toh SA, Sellers LA, Skepper JN, Koolwijk P, Leung HW, Yeung HW, Wong RNS, Sasisekharan R, Fan TP. Modulating angiogenesis- the yin and the yang in ginseng. Circulation 2004; 104: 1219-1225

20. Sengupta S, Sellers LA, Gherardi E, Sasisekharan R, Fan TP. Nitric oxide modulates hepatocyte growth factor induced angiogenesis. Angiogenesis 2004; 7: 285-94

21. Sengupta S, Eavarone DA, Capila I, Zhao G, Watson N, Kiziltepe T, Sasisekharan R. Novel cancer therapy through temporal targeting of both tumor cells and neovasculature using a unique nanoscale delivery system. Nature 2005; 436: 568-72

This was the first study to describe a layer-by-layer nanoparticles for targeting different compartments of a tumor.

22. Sengupta S, Sasisekharan R. Exploiting nanotechnology to target cancer. Br. J. Cancer. 2007; 96:1315-9

23. Sorathyia A, Jucikas T, Piecewicz S, Sengupta S, Lio P. Searching for glycomics role in vasculogenesis. Lecture Notes in Bioinformatics. 2008; 198-209

24. Agarwal S, Sengupta S. Ranking genes by relevance to a disease. Proc. LSS. Comput. Syst. Bioinform Conf. 2009; 37-46

25. Harfouche R, Basu S, Soni S, Hentschel D, Mashelkar RA, Sengupta S. Nanoparticle-mediated targeting of phosphatidylinositol-3-kinase signaling inhibits angiogenesis. Angiogenesis 2009; 12: 325-38

26. Chaudhuri P, Paraskar A, Soni S, Mashelkar RA, Sengupta S. Fullerenol-cytotoxic conjugates for cancer chemotherapy. ACS Nano. 2009; 3: 2505-14

27. Harfouche R, Hentschel D, Piecewicz, Basu S, Print C, Eavarone D, Kiziltepe T, Sasisekharan R, Sengupta S. Glycome and transcriptomal regulation of vasculogenesis. Circulation 2009; 120: 1883-92
This was the first study to demonstrate that the sulfation of GAGs is critical during differentiation of embryonic stem cells into vasculature.

28. Basu S, Harfouche R, Soni S, Chimote G, Mashelkar RA, Sengupta S. Nanoparticle-mediated targeting of mapk signaling predisposes tumor to chemotherapy. Proc. Natl. Acad. Sci. (U S A) 2009; 106: 7957-61

This was the first study to use nanoparticles for targeting signal transduction pathways.

29. Basu S, Chaudhuri P, Sengupta S. Targeting oncogenic signaling pathways by exploiting nanotechnology. Cell Cycle. 2009; 8: 3480-7

30. Chaudhuri P, Soni S, Sengupta S. Single-walled carbon nanotube-conjugated chemotherapy exhibit increased therapeutic index in melanoma. Nanotechnology. 2010; 21: 025102

31. Chaudhuri P, Harfouche R, Soni S, Hentschel DM, Sengupta S. Shape effect of carbon nanovectors on angiogenesis. ACS Nano. 2010; 4: 574-82

32. Agarwal S, Dugar D, Sengupta S. ranking chemical structures for drug discovery: a new machine learning approach. J. Chem. Inf. Model. 2010; 50: 716-31

33. Sinha Roy R, Soni S, Harfouche R, Vasudevan P, Holmes O, de Jonge H, Rowe A, Paraskar A, Hentschel DM, Gherardi E, Mashelkar RA, Sengupta S. Coupling growth factor engineering with nanotechnology for therapeutic angiogenesis. Proc. Natl. Acad. Sci. (USA) 2010; 107: 13608-13

This was the first study to use nanoparticles for targeting signal transduction pathways.

34. Paraskar A, Chin KT, Chaudhuri P, Muto KW, Berkowitz J, Handlogten MW, Alves NJ, Bilgicer B, Dinulescu DM, Mashelkar RA, Sengupta S. Harnessing structure-activity relationship to engineer a novel cisplatin nanoparticle for improved antitumor efficacy. Proc. Natl. Acad. Sci. (USA) 2010; 107: 12435-40

35. Banerjee D, Harfouche R, Sengupta S. Targeting angiogenesis using nanotechnology. Vasc. Cell 2011; 3: 3

36. Kohandel M, Haselwandter C, Kardar M, Sengupta S, Sivaloganathan S. Quantitative model for efficient temporal targeting of tumor cells and neovasculature. Comput. Math. Methods. Med. 2011; 790721

37. Sengupta P, Basu S, Sengupta S. Targeting signal transduction pathways in cancer using nanotechnology. Current Drug Deliv. 2011; 8: 254-60

38. Piecewicz S, Sengupta S. The dynamic glycome microenvironment and stem cell differentiation into vasculature. Stem Cell and Development 2011; 20: 749-58

39. Roy RS, Roy B, Sengupta S. Emerging technologies for enabling proangiogenic therapy. Nanotechnology. 2011; 22: 494004

40. Banerjee D, Sengupta S. Nanoparticles in cancer chemotherapy. Prog. Mol. Biol. Transl. Sci. 2011; 104: 489-507

41. Paraskar A, Soni S, Basu S, Amarasiriwardena CJ, Lupoli N, Srivats S, Roy RS, Sengupta S. Rationally engineered polymeric cisplatin nanoparticles for improved antitumor efficacy. Nanotechnology. 2011; 22: 265101

42. Piecewicz SM, Pandey A, Roy B, Hua Xiang S, Zetter BR, Sengupta S. Insulin-like growth factors promote vasculogenesis in embryonic stem cells. PLoS One. 2012; 7: e32191

43. Sengupta P, Basu S, Soni S, Pandey A, Oh M, Chin KT, Paraskar AS, Roy B, Sarangi S, Connor Y, Sabbisetti V, Kopparam J, Amarasiriwardena C, Jayawardene I, Lupoli N, Dinulescu DM, Bonventre JV, Mashelkar RA, Sengupta S. A cholesterol-tethered platinum ii-based supramolecular nanoparticle increases antitumor efficacy and reduces nephrotoxicity. Proc. Natl. Acad. Sci. (USA), 2012; 109: 11294-9

Here we described the use of SAR in designing an effective Pt-based nanoparticle.

44. Papa AL, Basu S, Sengupta P, Banerjee D, Sengupta S, Harfouche R. mechanistic studies of gemcitabine-loaded nanoplatforms in resistant pancreatic cancer cells. BMC Cancer. 2012; 12: 419

45. Paraskar A, Soni S, Roy B, Papa AL, Sengupta S. Rationally designed oxaliplatin nanoparticle for enhanced antitumor efficacy. Nanotechnology. 2012; 23: 075103

46. Sarangi S, Pandey A, Papa AL, Sengupta P, Kopparam J, Dadwal U, Basu S, Sengupta S. P2Y12 Receptor inhibition augments cytotoxic effects of cisplatin in breast cancer. Med. Oncol. 2013; 30: 567

47. Kulkarni AK, Roy B, Rao PS, Wyant GA, Mahmoud A, Ramachandran M, Sengupta P, Goldman A, Kotamraju VR, Basu B, Mashelkar RA, Ruoslahti E, Dinulescu DM, Sengupta S. Supramolecular nanoparticles that target phosphatidylinositol-3-kinase overcome insulin resistance and exert pronounced antitumor efficacy. Cancer Res. 2013; 73: 6987-97

48. Papa A, Sidiqui A, Balasubramanian SUA, Sarangi S, Luchette M, Sengupta S, Harfouche R. Pegylated liposomal gemcitabine: insights into a potential breast cancer therapeutic. Cell Oncol. 2013; 36: 449-57

49. Sengupta S, Kulkarni A. Design principles for clinical efficacy of cancer nanomedicine: a look into the basics. ACS Nano. 2013; 7: 2878-82

50. Sengupta S. Clinical translational challenges in nanomedicine. MRS Bull. 2014. 39: 259-264

51. Pandey A, Kulkarni A, Roy B, Goldman A, Sarangi S, Sengupta P, Phipps C, Kopparam J, Oh M, Basu S, Kohandel M, Sengupta S. Mathematically modeling the sequential application of a cytotoxic nanoparticle and a pi3k-inhibitor enhances anti-tumor efficacy. Cancer Res. 2014; 74: 675-85

52. Pandey A, Sarangi S, Chien K, Sengupta P, Papa AL, Basu S, Sengupta S. anti-platelet agents augment cisplatin nanoparticle cytotoxicity by enhancing tumor vasculature permeability and drug delivery. Nanotechnology. 2014; 25: 445101

53. Connor Y, Tekleab S, Nandakumar S, Walls C, Tekleab Y, Husain A, Gadish O, Sabbisetti V, Kaushik S, Sehrawat S, Kulkarni A, Dvorak H, Zetter B, Edelman E, Sengupta S. Physical nanoscale conduit-mediated communication between tumour cells and the endothelium modulates endothelial phenotype. Nature Commun. 2015; 6: 8671

54. Majumder B, Baraneedharan U, Thiyagarajan S, Radhakrishnan P, Narasimhan H, Dhandapani M, Brijwani N, Pinto DD, Prasath A, Shanthappa BU, Thayakumar A, Surendran R, Babu G, Shenoy AM, Kuriakose MA, Bergthold G, Horowitz P, Loda M, Beroukhim R, Agarwal S, Sengupta S*, Sundaram M*, Majumder PK*. Predicting clinical response to anticancer drugs using an ex vivo platform that captures tumour heterogeneity. Nature Commun. 2015; 6: 6169 (*equal senior contribution)

55. Goldman A. Majumder B, Dhawan A, Ravi S, Goldman D, Kohandel M, Majumder MK, Sengupta S. Temporally sequenced anticancer drugs overcome adaptive resistance by targeting a vulnerable chemotherapy-induced phenotypic transition. Nature Commun. 2015; 6: 6139

56. Sinha M, Sadhasivam S, Bhattacharyya A, Jain S, Ghosh S, Arndt KA, Dover JS, Sengupta S. Antibiotic-resistant acne: getting under the skin. Semin Cutan Med Surg. 2016; 35: 62-7

57. Boareto M, Jolly MK, Goldman A, Pietilä M, Mani SA, Sengupta S, Ben-Jacob E, Levine H, Onuchic JN. Notch-jagged signalling can give rise to clusters of cells exhibiting a hybrid epithelial/mesenchymal phenotype. J R Soc Interface. 2016; 13pii: 20151106

58. Molavian HR, Goldman A, Phipps CJ, Kohandel M, Wouters BG, Sengupta S, Sivaloganathan S. Drug-induced reactive oxygen species (ROS) rely on cell membrane properties to exert anticancer effects. Sci Rep. 2016; 6: 27439

59. Sadhasivam S, Sinha M, Saini S, Kaur SP, Gupta T, Sengupta S, Ghosh S, Sardana K. Heterogeneity and antibiotic resistance in Propionibacterium acnes strains and its therapeutic implications: blurring the lines between commensal and pathogenic phylotypes. Dermatol Ther. 2016. doi: 10.1111/dth.12391

60. Kulkarni AA, Rao P, Natarajan S, Goldman A, Sabbisetti V, Khater Y, Korimerla N, Mashelkar R, Sengupta S. “Reporter nanoparticle that monitors its anticancer efficacy in real time.”, Proc Natl Acad Sci U S A, 2016; 1: E2104-13
Editor’s Choice article on the above publication:

Kostic M. Seeing is believing. Cell Chemical Biology. 2016; 23: 428

Editorial survey on the above article:

Atala A. Urological Survey on Re: Reporter Nanoparticle that Monitors its Anticancer Efficacy in Real Time. The Journal of Urology. 2016; 196; 1313-1314

61. Kulkarni AA, Natarajan SK, Chandrasekar V, Pandey P, Sengupta S. “Combining immune checkpoint inhibitors and kinase-inhibiting supramolecular therapeutics for enhanced anti-cancer efficacy”, ACS Nano. 2016; 10: 9227–9242

62. Kulkarni AA, Pandey P, Rao P. S., Wyant G., Mahmoud A, Goldman A, Kotamraju VR, Ruoslahti E, Dinulescu D, Roy S, Sengupta S. “Algorithm for designing nanoscale supramolecular therapeutics with increased anticancer efficacy”, ACS Nano. 2016; 10: 8154-68.

Perspective article on the above publication:

Decuzzi P. Facilitating the Clinical Integration of Nanomedicines: The Roles of Theoretical and Computational Scientists, ACS Nano. 2016 10 (9), 8133-8138

63. Goldman A, Kulkarni AA, Kohandel M, Pandey PR, Natarajan S, Ravi S, Sabbisetti S, Sengupta S. “Rationally designed 2-in-1 nanoparticles can overcome adaptive resistance in cancer”, ACS Nano. 2016; 10: 5823-5824

64. Kulkarni AA, Vijaykumar VE, Natarajan SK, Sengupta S, Sabbisetti VS. “Sustained inhibition of cmet-vegfr2 signaling using liposome-mediated delivery increases efficacy and reduces toxicity in kidney cancer”, Nanomedicine: Nanotechnology, Biology and Medicine. 2016; 12: 1853-1861

65. Calibasi Kocal G, Güven S, Foygel K, Goldman A, Chen P, Sengupta S, Paulmurugan R, Baskin Y, Demirci U. Dynamic microenvironment induces phenotypic plasticity of esophageal cancer cells under flow. Sci Rep. 2016; 6: 38221

66. Gupta N, Kancharla J, Kaushik S, Ansari A, Hossain S, Goyal R, Pandey M, Sivaccumar J, Hussain S, Sarkar A, Sengupta A, Mandal SK, Roy M, Sengupta S. Development of a facile antibody-drug conjugate platform for increased stability and homogeneity. Chemical Sciences. 2017; 8: 2387-2395

67. Bhattacharyya A, Jain N, Prasad S, Jain S, Yadav V, Ghosh S, Sengupta S. Evaluation of therapeutic potential of vb-001, a leave-on formulation, for the treatment of moderate adherent dandruff. BMC Dermatol. 2017; 17: 5

68. Sengupta S. Cancer nanomedicine: lessons for immuno-oncology. Trends in Cancer. 2017 (In press)

69. Kulkarni A, et al. A designer self-assembled supramolecule amplifies macrophage immune responses against aggressive cancer. Nature Biomedical Engineering. 2018; 2: 589-599

News and Views by

Heather H. Gustafson & Suzie H. Pun Instructing macrophages to fight cancer. Nature Biomedical Engineeringvolume 2, pages559–561 (2018

70. Ghosh S, et al. A Rationally Designed Multifunctional Antibiotic for the Treatment of Drug-Resistant Acne. J Invest Dermatol. 2018;138(6):1400-1408

Book chapters, monographs

71. Sengupta S, Fan T-P D. Immunity. In The Oxford Companion to the Body. Blakemore C and Jennett S, editors. Oxford, UK: Oxford University Press, 2001. pp 86

72. Sengupta S, Fan T-P D. Autoimmune diseases. In The Oxford Companion to the Body. Blakemore C and Jennett S, editors. Oxford UK: Oxford University Press, 2001. pp 54-55

73. Sengupta S, Gupta S K. Angiogenesis: Concepts and research methodologies. In Pharmacology and Therapeutics in the New Millennium. Gupta SK, editor. New Delhi, India: Springer, 2001. pp.191-204

74. Sengupta S. Angiogenesis. In Drug Screening Methods. Gupta SK, editor. New Delhi, India: Jaypee Brothers Medical Publishers, 2009. pp 99-115.

75. Mashelkar RA, Patwardhan B, Sengupta S. Emerging innovation practices and policies for the healthcare needs of resource-poor people. Global Forum Update on Research for Health. 2009. 6: pp 153-156.

76. Chaudhuri P, Harfouche R, Sengupta S. The Bittersweet Promise of Glycobiology. In Biomarkers: In Medicine, Drug Discovery, and Environmental Health. Vaidya VS and Bonventre JV, editors. Hoboken N.J.: Wiley Press, 2010. pp 75-88.

77. Banerjee D, Sengupta S. Nanoparticles in Cancer Chemotherapy. In Nanoparticles in translational science and medicine. Villaverde A, editor. Vol. 104 in the series: Progress in molecular biology and translational science: Waltham, MA: Academic Press. 2011. pp 489-504

Selected conference papers

78. Piecewicz S, Sengupta S, Hentschel DM. Chemical genetic analysis of glycome regulation in vasculogenesis. Experimental Biology Conference, 2007. Washington D.C.

This paper was selected as one of the four finalists for the ASPET best paper award

79. Piecewizc S, Harfouche R, Hentschel D, Basu S, Sengupta S. A novel embryonic stem cell differentiation system for high-throughput antiangiogenesis screening. Experimental Biology, 2009. New-Orleans, Louisiana. Published in FASEB J. 2009: 23: 756.11

This submission was selected for the best paper award by ASPET

80. Sinha-Roy R, Soni S, Harfouche R, Vasudevan PR, Paraskar A, Sengupta S. Integrating novel protein engineering and nanotechnology for therapeutic angiogenesis. Experimental Biology Meeting, 2010. Published in FASEBJ. 2010; 24: 518

This submission was selected as a finalist for the best paper award

81. Connor Y, Harfouche R, Liu C, Oh M, Sengupta S. Modeling interactions between endothelial cells and metastatic breast cancer cells in a three-dimensional culture. AACR 101st Annual Meeting, Washington, DC 2010; Abstract 4813

This submission was selected for a spotlight presentation

82. Connor YD, Tekleab S, Gill NK, Bharat D, Lloyd T, Walls CR, Sengupta S. Intercellular transfer between metastatic breast cancer and the endothelium mediated by tunneling nanotubes. AACR Annual Meeting, Chicago, IL, 2012. Published in Cancer Res. 2012; 72: 4222

Connor YD Awarded the AACR Minority Scholar in Training Award for this paper

83. Kulkarni AA, Rao P, Goldman A, Sengupta S. Computationally-inspired engineering of supra-molecular taxane nanoparticles. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Published in Cancer Res. 2014; 74 (19 Suppl): Abstract: 5419.

Kulkarni AA was awarded an AACR Bristol-Myers-Squibb Scholar-in-Training prize from AACR for this paper

84. Roy M, Hossain SKS, Sarkar A, Sengupta A, Gupta A, Hussain S, Ansari A, Mylavarapu S, Sengupta S. IO125, a novel pt-based supramolecular therapeutic exhibits increased anti-cancer efficacy compared with oxaliplatin. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research, 2014; San Diego, CA. Published in Cancer Res. 2014; 74 (19 Suppl): Abstract: 4483

85. Kulkarni A, Rao P, Goldman A, Sengupta S. Targeting chemotherapy induced adaptive resistance using hybrid nanoparticles (LB577). Experimental Biology Meeting, San Diego, CA, April 2014. Published in The FASEB Journal, 2014; 28: LB577

Ashish Kulkarni was awarded a Young Scientist Travel Award for this paper

86. Sadhasivam S, Saini S, Kaur SP, Gupta T, Sardana K, Buchta R, Sengupta S, Ghosh S. Analysis of antibiotic resistance of propionibacterium acnes and other bacterial populations in the skin microbiomes of acne vulgaris patients in india. ICAAC/ICC, 2015, San Diego, California

87. Gupta N, Kancharla J, Kaushik S, Hossain S, Sarkar A, Sengupta A, Roy M, Sengupta S. Supramolecular assembly of antibody-drug conjugates using cordlink platform for targeted drug delivery. AACR 2015, Abstract Number: 649

88. Sengupta A, Mylavarapu S, Kumari S, Hossain S, Heeralal B, Gupta N, Sarkar A, Ansari A, Velpandian T, Roy M, Sengupta S. A novel supramolecular platinum chemotherapy being developed in triple-negative breast cancer. ASCO Breast Cancer Symposium, Abstract number 155134. 2015, San Diego, CA, USA

89. Roy M, Sengupta A, Sarkar A, Mylavarapu S, Modi S, Gupta N, Heeralal B, Hossain S, Ansari A, Pandey M, Yadav Y, Sengupta S. Designing a novel platinum chemotherapeutic (io-125) for treatment of breast cancer. San Antonio Breast Cancer Symposium, 2015, Program Number: P5-03-03, San Antonio, TX, USA

90. Bhattacharyya A, Sinha M, Sadhasivam S, Patel RS, Mandal D, Ghosh S, Sengupta S. A mechanistic and translational study of the antimicrobial effects of molecular replacement in malassezia. ICAAC/ICC, 2015, San Diego, CA, USA

91. Ghosh S, Sinha M, Sadhasivam S, Usharani D, Reddy S, Bhattacharyya A, Mishra M, Saini S, Kumar D, Patel RS, Ghosh S, Buchta R, Sengupta S. A novel antibiotic with reduced propensity to develop resistance. ICAAC/ICC, 2015, San Diego, CA, USA

92. Sadhasivam S, Ghosh S, Sinha M, Reddy S, Bhattacharyya A, Mishra M, Saini S, Kumar D, Patel RS, Ghosh S, Buchta R, Sengupta S. Antibiotic resistance crisis: a novel approach towards developing an effective regime. 5th Annual Conference of the Clinical Infectious Diseases Society, (CIDSCON) 2015, New Delhi, India

93. Kulkarni A, Pandey P, Rao P, Goldman G, Roy S, Sengupta S. Engineering of supramolecular taxane nanoparticles by computationally modeling drug-lipid bilayer interactions. Experimental Biology Meeting, 2015, Boston, MA. The FASEB Journal vol. 29 no. 1 Supplement 620.7

Kulkarni A awarded Young Scientist Travel Award for this paper

94. Chandrasekar V, Natarajan SK, Sengupta S, Kulkarni A. A. “Supramolecular fusion nanotherapeutic- mediated synergistic inhibition of pi3k and mek pathways”, AACR Annual Meeting, 2016, New Orleans, LA

This paper was selected for the best poster prize to Chandrasekar V

95. Natarajan S, Sengupta S, Kulkarni AA. “2-in-1 ‘Sniper’ nanomedicines rescue dendritic cells by two pronged inhibition of jak2/stat-3 and p38 mapk pathways”, AACR Annual Meeting, New Orleans, LA, 2016.

96. Kulkarni AA, Sabbisetti V, Sengupta S. “Supramolecular nanoparticles that target mapk pathway synergizes with immune checkpoint inhibitor in melanoma”, AACR Annual Meeting, Philadelphia, PA, 2015.

Kulkarni AA was awarded the AACR Scholar-in-Training award for this paper