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.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
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.
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.
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.
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.
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.
Ballinger, A., and Peikin, S.R. (2002). Orlistat: its current status as an antiobesity drug. Eur J Pharmacol 440, 109–117.
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.
Bartelt, A., and Heeren, J. (2014). Adipose tissue browning and metabolic health. Nat Rev Endocrinol 10, 24–36.
Cao, Y. (2007). Angiogenesis modulates adipogenesis and obesity. J Clin Invest 117, 2362–2368.
Cao, Y. (2013). Angiogenesis and vascular functions in modulation of obesity, adipose metabolism, and insulin sensitivity. Cell Metab 18, 478–489.
Carmeliet, P., and Jain, R.K. (2000). Angiogenesis in cancer and other diseases. Nature 407, 249–257.
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.
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.
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.
Friedman, J.M. (2009). Causes and control of excess body fat. Nature 459, 340–342.
George, M., Rajaram, M., and Shanmugam, E. (2014). New and emerging drug molecules against obesity. J Cardiovasc Pharmacol Ther 19, 65–76.
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.
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.
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.
Harms, M., and Seale, P. (2013). Brown and beige fat: development, function and therapeutic potential. Nat Med 19, 1252–1263.
Haslam, D. (2016). Weight management in obesity—past and present. Int J Clin Pract 70, 206–217.
Heymsfield, S.B., and Wadden, T.A. (2017). Mechanisms, pathophysiology, and management of obesity. N Engl J Med 376, 254–266.
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.
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.
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.
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.
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.
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.
Kajimura, S., Spiegelman, B.M., and Seale, P. (2015). Brown and beige fat: physiological roles beyond heat generation. Cell Metab 22, 546–559.
Kakkar, A.K., and Dahiya, N. (2015). Drug treatment of obesity: current status and future prospects. Eur J Intern Med 26, 89–94.
Kang, J.G., and Park, C.Y. (2012). Anti-obesity drugs: a review about their effects and safety. Diabetes Metab J 36, 13–25.
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.
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.
Kushner, R.F. (2008). Anti-obesity drugs. Expert Opin Pharmacother 9, 1339–1350.
Kushner, R.F., and Ryan, D.H. (2014). Assessment and lifestyle management of patients with obesity. JAMA 312, 943–952.
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.
Lu, Y., Aimetti, A.A., Langer, R., and Gu, Z. (2016). Bioresponsive materials. Nat Rev Mater 2, 16075.
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.
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.
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.
Mun, E.C., Blackburn, G.L., and Matthews, J.B. (2001). Current status of medical and surgical therapy for obesity. Gastroenterology 120, 669–681.
Mura, S., and Couvreur, P. (2012). Nanotheranostics for personalized medicine. Adv Drug Deliver Rev 64, 1394–1416.
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.
World Health Organization. (2014). Obesity and overweight. J Physiother 60, 114.
Parveen, S., Misra, R., and Sahoo, S.K. (2012). Nanoparticles: a boon to drug delivery, therapeutics, diagnostics and imaging. Nanomedicine 8, 147–166.
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.
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.
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.
Schneider, B.E., and Mun, E.C. (2005). Surgical management of morbid obesity. Diabetes Care 28, 475–480.
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.
Sun, W., Hu, Q., Ji, W., Wright, G., and Gu, Z. (2017). Leveraging physiology for precision drug delivery. Physiol Rev 97, 189–225.
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.
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.
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.
Wadden, T.A., Butryn, M.L., and Wilson, C. (2007). Lifestyle modification for the management of obesity. Gastroenterology 132, 2226–2238.
Wiedmer, P., Nogueiras, R., Broglio, F., D’Alessio, D., and Tschöp, M.H. (2007). Ghrelin, obesity and diabetes. Nat Rev Endocrinol 3, 705–712.
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.
Wu, J., Cohen, P., and Spiegelman, B.M. (2013). Adaptive thermogenesis in adipocytes: is beige the new brown? Genes Dev 27, 234–250.
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.
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.
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.
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.
Yu, J., Zhang, Y., Kahkoska, A.R., and Gu, Z. (2017). Bioresponsive transcutaneous patches. Curr Opin Biotech 48, 28–32.
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.
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.
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.
Acknowledgements
This work was supported by the grant from Sloan Research Fellowship.
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Zhang, Y., Yu, J., Qiang, L. et al. Nanomedicine for obesity treatment. Sci. China Life Sci. 61, 373–379 (2018). https://doi.org/10.1007/s11427-017-9257-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11427-017-9257-1