Nanomedicine for obesity treatment

Review Thematic Issue: Nanotechnology and nanomedicine
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Abstract

Obesity, as a chronic condition, has been a serious public health issue over the last decades both in the affluent Western world and developing countries. As reported, the risk of several serious diseases increases with weight gain, including type 2 diabetes, coronary heart disease, cancer, and respiratory diseases. In addition to lifestyle modifications, pharmacotherapy has become an important strategy to control weight gain. However, most of the anti-obesity drugs often show poor outcome for weight-loss and cause severe adverse effects. This review surveys recent advances in nanomedicine as an emerging strategy for obesity treatment with an emphasis on the enhanced therapeutic efficiency and minimized side effects. The insights for future development are also discussed.

Keywords

drug delivery nanomedicine obesity browning fat absorption energy expenditure 

Notes

Acknowledgements

This work was supported by the grant from Sloan Research Fellowship.

References

  1. Ahima, R.S., Prabakaran, D., Mantzoros, C., Qu, D., Lowell, B., Maratos-Flier, E., and Flier, J.S. (1996). Role of leptin in the neuroendocrine response to fasting. Nature 382, 250–252.CrossRefPubMedGoogle Scholar
  2. Almeida, M.A., Nadal, J.M., Grassiolli, S., Paludo, K.S., Zawadzki, S.F., Cruz, L., Paula, J.P., and Farago, P.V. (2014). Enhanced gastric tolerability and improved anti-obesity effect of capsaicinoids-loaded PCL microparticles. Mater Sci Eng-C 40, 345–356.CrossRefGoogle Scholar
  3. Andrade, S., Pinho, F., Ribeiro, A., Carreira, M., Casanueva, F., Roy, P., and Monteiro, M. (2013). Immunization against active ghrelin using virus-like particles for obesity treatment. Curr Pharm Des 19, 6551–6558.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Atasoy, D., Betley, J.N., Li, W.P., Su, H.H., Sertel, S.M., Scheffer, L.K., Simpson, J.H., Fetter, R.D., and Sternson, S.M. (2014). A genetically specified connectomics approach applied to long-range feeding regulatory circuits. Nat Neurosci 17, 1830–1839.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Bakh, N.A., Cortinas, A.B., Weiss, M.A., Langer, R.S., Anderson, D.G., Gu, Z., Dutta, S., and Strano, M.S. (2017). Glucose-responsive insulin by molecular and physical design. Nat Chem 9, 937–943.CrossRefPubMedGoogle Scholar
  6. Ballinger, A., and Peikin, S.R. (2002). Orlistat: its current status as an antiobesity drug. Eur J Pharmacol 440, 109–117.CrossRefPubMedGoogle Scholar
  7. Barnhart, K.F., Christianson, D.R., Hanley, P.W., Driessen, W.H.P., Bernacky, B.J., Baze, W.B., Wen, S., Tian, M., Ma, J., Kolonin, M.G., et al. (2011). A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys. Sci Transl Med 3, 10-8ra112.CrossRefGoogle Scholar
  8. Bartelt, A., and Heeren, J. (2014). Adipose tissue browning and metabolic health. Nat Rev Endocrinol 10, 24–36.CrossRefPubMedGoogle Scholar
  9. Cao, Y. (2007). Angiogenesis modulates adipogenesis and obesity. J Clin Invest 117, 2362–2368.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Cao, Y. (2013). Angiogenesis and vascular functions in modulation of obesity, adipose metabolism, and insulin sensitivity. Cell Metab 18, 478–489.CrossRefPubMedGoogle Scholar
  11. Carmeliet, P., and Jain, R.K. (2000). Angiogenesis in cancer and other diseases. Nature 407, 249–257.CrossRefPubMedGoogle Scholar
  12. Chen, Y.L., Zhu, S., Zhang, L., Feng, P.J., Yao, X.K., Qian, C.G., Zhang, C., Jiang, X.Q., and Shen, Q.D. (2016). Smart conjugated polymer nanocarrier for healthy weight loss by negative feedback regulation of lipase activity. Nanoscale 8, 3368–3375.CrossRefPubMedGoogle Scholar
  13. Clemmensen, C., Chabenne, J., Finan, B., Sullivan, L., Fischer, K., Küchler, D., Sehrer, L., Ograjsek, T., Hofmann, S.M., Schriever, S.C., et al. (2014). GLP-1/glucagon coagonism restores leptin responsiveness in obese mice chronically maintained on an obesogenic diet. Diabetes 63, 1422–1427.CrossRefPubMedGoogle Scholar
  14. des Rieux, A., Pourcelle, V., Cani, P.D., Marchand-Brynaert, J., and Préat, V. (2013). Targeted nanoparticles with novel non-peptidic ligands for oral delivery. Adv Drug Deliver Rev 65, 833–844.CrossRefGoogle Scholar
  15. Friedman, J.M. (2009). Causes and control of excess body fat. Nature 459, 340–342.CrossRefPubMedGoogle Scholar
  16. George, M., Rajaram, M., and Shanmugam, E. (2014). New and emerging drug molecules against obesity. J Cardiovasc Pharmacol Ther 19, 65–76.CrossRefPubMedGoogle Scholar
  17. Ghamari-Langroudi, M., Digby, G.J., Sebag, J.A., Millhauser, G.L., Palomino, R., Matthews, R., Gillyard, T., Panaro, B.L., Tough, I.R., Cox, H. M., et al. (2015). G-protein-independent coupling of MC4R to Kir7.1 in hypothalamic neurons. Nature 520, 94–98.CrossRefPubMedPubMedCentralGoogle Scholar
  18. Gu, Z., Aimetti, A.A., Wang, Q., Dang, T.T., Zhang, Y., Veiseh, O., Cheng, H., Langer, R.S., and Anderson, D.G. (2013a). Injectable nano-network for glucose-mediated insulin delivery. ACS Nano 7, 4194–4201.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Gu, Z., Dang, T.T., Ma, M., Tang, B.C., Cheng, H., Jiang, S., Dong, Y., Zhang, Y., and Anderson, D.G. (2013b). Glucose-responsive microgels integrated with enzyme nanocapsules for closed-loop insulin delivery. ACS Nano 7, 6758–6766.CrossRefPubMedGoogle Scholar
  20. Harms, M., and Seale, P. (2013). Brown and beige fat: development, function and therapeutic potential. Nat Med 19, 1252–1263.CrossRefPubMedGoogle Scholar
  21. Haslam, D. (2016). Weight management in obesity—past and present. Int J Clin Pract 70, 206–217.CrossRefPubMedPubMedCentralGoogle Scholar
  22. Heymsfield, S.B., and Wadden, T.A. (2017). Mechanisms, pathophysiology, and management of obesity. N Engl J Med 376, 254–266.CrossRefPubMedGoogle Scholar
  23. Hossen, M.N., Kajimoto, K., Akita, H., Hyodo, M., Ishitsuka, T., and Harashima, H. (2010). Ligand-based targeted delivery of a peptide modified nanocarrier to endothelial cells in adipose tissue. J Control Release 147, 261–268.CrossRefPubMedGoogle Scholar
  24. Hossen, M.N., Kajimoto, K., Akita, H., Hyodo, M., and Harashima, H. (2012). Vascular-targeted nanotherapy for obesity: unexpected passive targeting mechanism to obese fat for the enhancement of active drug delivery. J Control Release 163, 101–110.CrossRefPubMedGoogle Scholar
  25. Hossen, M.N., Kajimoto, K., Akita, H., Hyodo, M., and Harashima, H. (2013). A comparative study between nanoparticle-targeted therapeutics and bioconjugates as obesity medication. J Control Release 171, 104–112.CrossRefPubMedGoogle Scholar
  26. Jackson, V.M., Breen, D.M., Fortin, J.P., Liou, A., Kuzmiski, J.B., Loomis, A.K., Rives, M.L., Shah, B., and Carpino, P.A. (2015). Latest approaches for the treatment of obesity. Expert Opin Drug Discov 10, 825–839.CrossRefPubMedGoogle Scholar
  27. Jiang, C., Kuang, L., Merkel, M.P., Yue, F., Cano-Vega, M.A., Narayanan, N., Kuang, S., and Deng, M. (2015). Biodegradable polymeric micro-sphere-based drug delivery for inductive browning of fat. Front Endocrinol 6, 169.CrossRefGoogle Scholar
  28. Jiang, C., Cano-Vega, M.A., Yue, F., Kuang, L., Narayanan, N., Uzunalli, G., Merkel, M.P., Kuang, S., and Deng, M. (2017). Dibenzazepineloaded nanoparticles induce local browning of white adipose tissue to counteract obesity. Mol Ther 25, 1718–1729.CrossRefPubMedGoogle Scholar
  29. Kajimura, S., Spiegelman, B.M., and Seale, P. (2015). Brown and beige fat: physiological roles beyond heat generation. Cell Metab 22, 546–559.CrossRefPubMedPubMedCentralGoogle Scholar
  30. Kakkar, A.K., and Dahiya, N. (2015). Drug treatment of obesity: current status and future prospects. Eur J Intern Med 26, 89–94.CrossRefPubMedGoogle Scholar
  31. Kang, J.G., and Park, C.Y. (2012). Anti-obesity drugs: a review about their effects and safety. Diabetes Metab J 36, 13–25.CrossRefPubMedPubMedCentralGoogle Scholar
  32. Kolonin, M.G., Saha, P.K., Chan, L., Pasqualini, R., and Arap, W. (2004). Reversal of obesity by targeted ablation of adipose tissue. Nat Med 10, 625–632.CrossRefPubMedGoogle Scholar
  33. Kupferschmidt, N., Csikasz, R.I., Ballell, L., Bengtsson, T., and Garcia-Bennett, A.E. (2014). Large pore mesoporous silica induced weight loss in obese mice. Nanomedicine 9, 1353–1362.CrossRefPubMedGoogle Scholar
  34. Kushner, R.F. (2008). Anti-obesity drugs. Expert Opin Pharmacother 9, 1339–1350.CrossRefPubMedGoogle Scholar
  35. Kushner, R.F., and Ryan, D.H. (2014). Assessment and lifestyle management of patients with obesity. JAMA 312, 943–952.CrossRefPubMedGoogle Scholar
  36. Ledoux, S., Queguiner, I., Msika, S., Calderari, S., Rufat, P., Gasc, J.M., Corvol, P., and Larger, E. (2008). Angiogenesis associated with visceral and subcutaneous adipose tissue in severe human obesity. Diabetes 57, 3247–3257.CrossRefPubMedPubMedCentralGoogle Scholar
  37. Lu, Y., Aimetti, A.A., Langer, R., and Gu, Z. (2016). Bioresponsive materials. Nat Rev Mater 2, 16075.CrossRefGoogle Scholar
  38. Ma, L., Liu, T.W., Wallig, M.A., Dobrucki, I.T., Dobrucki, L.W., Nelson, E. R., Swanson, K.S., and Smith, A.M. (2016). Efficient targeting of adipose tissue macrophages in obesity with polysaccharide nanocarriers. ACS Nano 10, 6952–6962.CrossRefPubMedGoogle Scholar
  39. Malik, V.S., Willett, W.C., and Hu, F.B. (2013). Global obesity: trends, risk factors and policy implications. Nat Rev Endocrinol 9, 13–27.CrossRefPubMedGoogle Scholar
  40. Marrache, S., and Dhar, S. (2012). Engineering of blended nanoparticle platform for delivery of mitochondria-acting therapeutics. Proc Natl Acad Sci USA 109, 16288–16293.CrossRefPubMedPubMedCentralGoogle Scholar
  41. Mun, E.C., Blackburn, G.L., and Matthews, J.B. (2001). Current status of medical and surgical therapy for obesity. Gastroenterology 120, 669–681.CrossRefPubMedGoogle Scholar
  42. Mura, S., and Couvreur, P. (2012). Nanotheranostics for personalized medicine. Adv Drug Deliver Rev 64, 1394–1416.CrossRefGoogle Scholar
  43. Musthaba, S., Ahmad, S., Ahuja, A., Ali, J., and Baboota, S. (2009). Nano approaches to enhance pharmacokinetic and pharmacodynamic activity of plant origin drugs. Curr Nanosci 5, 344–352.CrossRefGoogle Scholar
  44. World Health Organization. (2014). Obesity and overweight. J Physiother 60, 114.Google Scholar
  45. Parveen, S., Misra, R., and Sahoo, S.K. (2012). Nanoparticles: a boon to drug delivery, therapeutics, diagnostics and imaging. Nanomedicine 8, 147–166.CrossRefPubMedGoogle Scholar
  46. Rodgers, R.J., Tschöp, M.H., and Wilding, J.P.H. (2012). Anti-obesity drugs: past, present and future. Dis Model Mech 5, 621–626.CrossRefPubMedPubMedCentralGoogle Scholar
  47. Rucker, D., Padwal, R., Li, S.K., Curioni, C., and Lau, D.C.W. (2007). Long term pharmacotherapy for obesity and overweight: updated metaanalysis. BMJ 335, 1194–1199.CrossRefPubMedPubMedCentralGoogle Scholar
  48. Sangwai, M., Sardar, S., and Vavia, P. (2014). Nanoemulsified orlistatembedded multi-unit pellet system (MUPS) with improved dissolution and pancreatic lipase inhibition. Pharmaceut Dev Tech 19, 31–41.CrossRefGoogle Scholar
  49. Schneider, B.E., and Mun, E.C. (2005). Surgical management of morbid obesity. Diabetes Care 28, 475–480.CrossRefPubMedGoogle Scholar
  50. Sohn, J.W., Harris, L.E., Berglund, E.D., Liu, T., Vong, L., Lowell, B.B., Balthasar, N., Williams, K.W., and Elmquist, J.K. (2013). Melanocortin 4 receptors reciprocally regulate sympathetic and parasympathetic preganglionic neurons. Cell 152, 612–619.CrossRefPubMedPubMedCentralGoogle Scholar
  51. Sun, W., Hu, Q., Ji, W., Wright, G., and Gu, Z. (2017). Leveraging physiology for precision drug delivery. Physiol Rev 97, 189–225.CrossRefGoogle Scholar
  52. Thovhogi, N., Sibuyi, N., Meyer, M., Onani, M., and Madiehe, A. (2015). Targeted delivery using peptide-functionalised gold nanoparticles to white adipose tissues of obese rats. J Nanopart Res 17, 112.CrossRefGoogle Scholar
  53. Trayhurn, P., and Beattie, J.H. (2001). Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ. Proc Nutr Soc 60, 329–339.CrossRefPubMedGoogle Scholar
  54. Voros, G., Maquoi, E., Demeulemeester, D., Clerx, N., Collen, D., and Lijnen, H.R. (2005). Modulation of angiogenesis during adipose tissue development in murine models of obesity. Endocrinology 146, 4545–4554.CrossRefPubMedGoogle Scholar
  55. Wadden, T.A., Butryn, M.L., and Wilson, C. (2007). Lifestyle modification for the management of obesity. Gastroenterology 132, 2226–2238.CrossRefPubMedGoogle Scholar
  56. Wiedmer, P., Nogueiras, R., Broglio, F., D’Alessio, D., and Tschöp, M.H. (2007). Ghrelin, obesity and diabetes. Nat Rev Endocrinol 3, 705–712.CrossRefGoogle Scholar
  57. Won, Y.W., Adhikary, P.P., Lim, K.S., Kim, H.J., Kim, J.K., and Kim, Y.H. (2014). Oligopeptide complex for targeted non-viral gene delivery to adipocytes. Nat Mater 13, 1157–1164.CrossRefPubMedGoogle Scholar
  58. Wu, J., Cohen, P., and Spiegelman, B.M. (2013). Adaptive thermogenesis in adipocytes: is beige the new brown? Genes Dev 27, 234–250.CrossRefPubMedPubMedCentralGoogle Scholar
  59. Xue, Y., Xu, X., Zhang, X.Q., Farokhzad, O.C., and Langer, R. (2016). Preventing diet-induced obesity in mice by adipose tissue transformation and angiogenesis using targeted nanoparticles. Proc Natl Acad Sci USA 113, 5552–5557.CrossRefPubMedPubMedCentralGoogle Scholar
  60. Yameen, B., Choi, W.I., Vilos, C., Swami, A., Shi, J., and Farokhzad, O.C. (2014). Insight into nanoparticle cellular uptake and intracellular targeting. J Control Release 190, 485–499.CrossRefPubMedPubMedCentralGoogle Scholar
  61. Yanovski, S., Dietz, W., Goodwin, N., Hill, J., PiSunyer, F., Rolls, B., Stern, J., Weinsier, R., Wilson, G., and Wing, R. (1996). Long-term pharmacotherapy in the management of obesity. JAMA 276, 1907–1915.CrossRefGoogle Scholar
  62. Yu, J., Zhang, Y., Ye, Y., DiSanto, R., Sun, W., Ranson, D., Ligler, F.S., Buse, J.B., and Gu, Z. (2015). Microneedle-array patches loaded with hypoxia-sensitive vesicles provide fast glucose-responsive insulin delivery. Proc Natl Acad Sci USA 112, 8260–8265.CrossRefPubMedPubMedCentralGoogle Scholar
  63. Yu, J., Zhang, Y., Kahkoska, A.R., and Gu, Z. (2017). Bioresponsive transcutaneous patches. Curr Opin Biotech 48, 28–32.CrossRefPubMedGoogle Scholar
  64. Zhang, Y., Chan, H.F., and Leong, K.W. (2013). Advanced materials and processing for drug delivery: the past and the future. Adv Drug Deliver Rev 65, 104–120.CrossRefGoogle Scholar
  65. Zhang, Y., Liu, Q., Yu, J., Yu, S., Wang, J., Qiang, L., and Gu, Z. (2017a). Locally induced adipose tissue browning by microneedle patch for obesity treatment. ACS Nano 11, 9223–9230.CrossRefPubMedGoogle Scholar
  66. Zhang, Y., Yu, J., Wang, J., Hanne, N.J., Cui, Z., Qian, C., Wang, C., Xin, H., Cole, J.H., Gallippi, C.M., Zhu, Y., and Gu, Z. (2017b). Thrombinresponsive transcutaneous patch for auto-anticoagulant regulation. Adv Mater 29, 1604043.CrossRefGoogle Scholar

Copyright information

© Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Joint Department of Biomedical EngineeringUniversity of North Carolina at Chapel Hill and North Carolina State UniversityRaleighUSA
  2. 2.Center for Nanotechnology in Drug Delivery and Division of Molecular Pharmaceutics, UNC Eshelman School of PharmacyUniversity of North Carolina at Chapel HillChapel HillUSA
  3. 3.Department of Pathology and Cell Biology, Naomi Berrie Diabetes CenterColumbia UniversityNew YorkUSA
  4. 4.Department of MedicineUniversity of North Carolina at Chapel HillChapel HillUSA

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