Adipocytolytic Polymer Nanoparticles for Localized Fat Reduction.

The demand for body fat reduction is increasing. However, conventional lipolytic approaches fail to control adipose tissue reduction and cause severe side effects in adjacent nonadipose tissues. A strategy to specifically reduce subcutaneous fat using adipocytolytic polymer nanoparticles in a minimally invasive manner is reported here. The polymer nanoparticles are designed to generate carbon dioxide gas when selectively absorbed by adipocytes. The carbon dioxide gas generated within late endosomes/lysosomes induces adipocytolysis, thereby reducing the number of cells. Localized injection of the adipocytolytic nanoparticles substantially reduces subcutaneous fat in a high-fat diet-induced obese mouse model, without significant changes in hematological or serum biochemical parameters. The adipocytolytic efficacy of the nanoparticles is also evaluated in a porcine model. This strategy addresses the need to develop safe and effective adipocytolytic agents using functional polymer nanoparticles.

[1]  M. Kolonin,et al.  Prohibitin Inactivation in Adipocytes Results in Reduced Lipid Metabolism and Adaptive Thermogenesis Impairment , 2021, Diabetes.

[2]  K. Braeckmans,et al.  Bubble Forming Films for Spatial Selective Cell Killing , 2021, Advanced materials.

[3]  K. Cherubini,et al.  Deoxycholic acid in the submental fat reduction: A review of properties, adverse effects, and complications , 2020, Journal of cosmetic dermatology.

[4]  M. Evans,et al.  Drug Therapy in Obesity: A Review of Current and Emerging Treatments , 2020, Diabetes Therapy.

[5]  M. Meyer,et al.  Nanotechnology advances towards development of targeted-treatment for obesity , 2019, Journal of Nanobiotechnology.

[6]  A. Singh,et al.  Pharmacotherapy in obesity: a systematic review and meta-analysis of randomized controlled trials of anti-obesity drugs , 2019, Expert review of clinical pharmacology.

[7]  Roger D Kamm,et al.  An on-chip model of protein paracellular and transcellular permeability in the microcirculation. , 2019, Biomaterials.

[8]  H. Ashrafian,et al.  Current treatments for obesity. , 2019, Clinical medicine.

[9]  Jie Fu,et al.  Silver nanoparticles inhibit beige fat function and promote adiposity , 2019, Molecular metabolism.

[10]  S. Lee,et al.  Can Gut Microbiota Modulation Be Used as a Practical Treatment for Obesity? , 2018, Journal of obesity & metabolic syndrome.

[11]  K. Lee,et al.  Carbon Dioxide-Generating PLG Nanoparticles for Controlled Anti-Cancer Drug Delivery , 2018, Pharmaceutical Research.

[12]  E. Raposio,et al.  A journey through liposuction and liposculture: Review , 2017, Annals of medicine and surgery.

[13]  R. Seabury,et al.  Severe neutrophilic dermatosis following submental deoxycholic acid administration , 2017, Clinical toxicology.

[14]  A Morabito,et al.  Subcutaneous fat loss is greater than visceral fat loss with diet and exercise, weight-loss promoting drugs and bariatric surgery: a critical review and meta-analysis , 2017, International Journal of Obesity.

[15]  P. Garcez,et al.  Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models , 2016, Viruses.

[16]  Sams M A Sadat,et al.  Effects of Size and Surface Charge of Polymeric Nanoparticles on in Vitro and in Vivo Applications , 2016 .

[17]  Kwangmeyung Kim,et al.  Theranostic gas-generating nanoparticles for targeted ultrasound imaging and treatment of neuroblastoma. , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[18]  K. Nouri,et al.  Non‐invasive subcutaneous fat reduction: a review , 2015, Journal of the European Academy of Dermatology and Venereology : JEADV.

[19]  K. Wooley,et al.  Polymeric Nanostructures for Imaging and Therapy. , 2015, Chemical reviews.

[20]  Solmaz Maleki Dizaj,et al.  Calcium carbonate nanoparticles as cancer drug delivery system , 2015, Expert opinion on drug delivery.

[21]  Xing Ma,et al.  A preloaded amorphous calcium carbonate/doxorubicin@silica nanoreactor for pH-responsive delivery of an anticancer drug. , 2015, Angewandte Chemie.

[22]  Ick Chan Kwon,et al.  pH-controlled gas-generating mineralized nanoparticles: a theranostic agent for ultrasound imaging and therapy of cancers. , 2015, ACS nano.

[23]  K. Lim,et al.  Oligopeptide complex for targeted non-viral gene delivery to adipocytes. , 2014, Nature materials.

[24]  Xiaoxiao Cai,et al.  Polymeric nanoparticles for a drug delivery system. , 2013, Current drug metabolism.

[25]  A. Xu,et al.  The inhibition of human bladder cancer growth by calcium carbonate/CaIP6 nanocomposite particles delivering AIB1 siRNA. , 2013, Biomaterials.

[26]  H. Harashima,et al.  Vascular-targeted nanotherapy for obesity: unexpected passive targeting mechanism to obese fat for the enhancement of active drug delivery. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[27]  V. Préat,et al.  PLGA-based nanoparticles: an overview of biomedical applications. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[28]  Suman Mishra,et al.  Prohibitin has an important role in adipocyte differentiation , 2012, International Journal of Obesity.

[29]  Junying Yuan,et al.  Cell death assays for drug discovery , 2011, Nature Reviews Drug Discovery.

[30]  J. Spiegel,et al.  Histologic evaluation of laser lipolysis comparing continuous wave vs pulsed lasers in an in vivo pig model. , 2011, Archives of facial plastic surgery.

[31]  L. Chernomordik,et al.  Cell-penetrating peptide induces leaky fusion of liposomes containing late endosome-specific anionic lipid. , 2010, Biophysical journal.

[32]  H. Harashima,et al.  Ligand-based targeted delivery of a peptide modified nanocarrier to endothelial cells in adipose tissue. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[33]  C. Elangbam.  Review Paper: Current Strategies in the Development of Anti-obesity Drugs and Their Safety Concerns , 2009, Veterinary pathology.

[34]  C. Kahn,et al.  Developmental Origin of Fat: Tracking Obesity to Its Source , 2007, Cell.

[35]  L. Brannon-Peppas,et al.  Nanoparticle and targeted systems for cancer therapy. , 2004, Advanced drug delivery reviews.

[36]  S. O’Rahilly,et al.  Regulation of adipose cell number in man. , 1997, Clinical science.