Polymeric nanomedicine for tumor-targeted combination therapy to elicit synergistic genotoxicity against prostate cancer

ACS Applied Materials & Interfaces
Qingqing YangYuan Huang

Abstract

To improve the therapeutic efficacy of anticancer combination therapy, we designed a nanoplatform based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers that allows covalent bonding of two chemotherapeutics acting via different anticancer mechanisms and that can enter target cells by receptor-mediated endocytosis. Doxorubicin (DOX) was covalently conjugated to a nanosized HPMA copolymer using a pH-sensitive hydrazone bond and 5-fluorouracil (5-Fu) was conjugated to the same backbone using an enzymatically degradable oligopeptide Gly-Phe-Leu-Gly sequence. Then, the conjugate was decorated with galectin-3 targeting peptide G3-C12 [P-(G3-C12)-DOX-Fu]. The two drugs showed similar in vitro release profiles, suggesting that they may be able to work synergistically in the codelivery system. In galectin-3 overexpressed PC-3 human prostate carcinoma cells, P-(G3-C12)-DOX-Fu surprisingly exhibited comparable cytotoxicity to free DOX at high concentration by increasing cell internalization and exerting synergistic genotoxic effects of cell cycle arrest, caspase-3 activation, and DNA damage. In mice bearing PC-3 tumor xenografts, the use of tumor-targeting ligand substantially enhanced the intracellular delivery of P-(G3-C12)-DOX-F...Continue Reading

References

Feb 1, 1990·Journal of Chemotherapy·E CortesiP Marchetti
May 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·R D OlsonR J Boucek
Jul 1, 1995·Stem Cells·M BinaschiG Capranico
Dec 16, 1998·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·H JoensuuR Huovinen
Jan 21, 2000·Journal of Controlled Release : Official Journal of the Controlled Release Society·K UlbrichB Ríhová
Mar 17, 2001·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·J JassemUNKNOWN Central & Eastern Europe and Israel Pacitaxel Breast Cancer Study Group
May 5, 2001·Journal of Controlled Release : Official Journal of the Controlled Release Society·T EtrychK Ulbrich
Sep 14, 2004·Nature·Sunil S KarhadkarPhilip A Beachy
Jul 20, 2006·DNA and Cell Biology·Kazuhiro IshikawaToshiyuki Saito
Feb 8, 2008·Nature Reviews. Cancer·Thomas HelledayRicky A Sharma
Jul 26, 2008·Nature Nanotechnology·Dan PeerRobert Langer
Jul 29, 2008·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Fang YuanYuan Huang
Feb 25, 2009·ACS Nano·P V AshaRaniSuresh Valiyaveettil
Jun 6, 2009·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Hana KrakovicováKarel Ulbrich
Aug 25, 2009·Advanced Drug Delivery Reviews·Francesca Greco, María J Vicent
Nov 19, 2009·Advanced Drug Delivery Reviews·Jindrich Kopecek, Pavla Kopecková
Nov 26, 2009·Advanced Drug Delivery Reviews·Karel Ulbrich, Vladimír Subr
Dec 3, 2009·Advanced Drug Delivery Reviews·Daniel B Pike, Hamidreza Ghandehari
Jan 13, 2010·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Yi-Fei ZhangQiang Zhang
Mar 12, 2011·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Tomáš EtrychKarel Ulbrich
May 28, 2011·Current Opinion in Cell Biology·Cecile BoscherIvan R Nabi
Jul 23, 2011·Journal of Translational Medicine·Paolo A Ascierto, Francesco M Marincola
Sep 29, 2011·Journal of Controlled Release : Official Journal of the Controlled Release Society·Twan LammersGert Storm
Oct 12, 2011·Journal of the American Chemical Society·Jin-Zhi DuJun Wang
Jun 19, 2012·Chemistry of Materials : a Publication of the American Chemical Society·Nate Larson, Hamidreza Ghandehari
Aug 3, 2012·The New England Journal of Medicine·Rita S MehtaGabriel N Hortobagyi
Nov 6, 2012·Advanced Drug Delivery Reviews·Jindřich Kopeček
Dec 25, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Rui ZhangJindřich Kopeček
Sep 18, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yan ZhouJindřich Kopeček
Jan 11, 2014·Molecular Pharmaceutics·Huiyuan WangYongzhuo Huang
Apr 22, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Jiyuan Yang, Jindřich Kopeček
May 27, 2014·Seminars in Cancer Biology·Simone Fulda

❮ Previous
Next ❯

Citations

Mar 12, 2016·Investigative and Clinical Urology·Vinoth-Kumar Lakshmanan
Apr 22, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Lian LiYuan Huang
May 18, 2016·Drug Development and Industrial Pharmacy·Huifeng DiChuanhai Dong
Jan 26, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Jieke YanHongwei Wang
Dec 23, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sonja DragojevicDrazen Raucher
Jan 11, 2018·International Journal of Molecular Sciences·Kamil WdowiakJerzy Wojnar
Aug 31, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Qiuxia YanYi Ma
Feb 27, 2018·Frontiers in Pharmacology·Tabassum Khan, Pranav Gurav
May 28, 2018·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Jie LiuPeihong Ni
Mar 17, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Ejaj AhmadSundeep Singh Saluja
Apr 16, 2021·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Lital CohenYehuda G Assaraf
Dec 21, 2017·ACS Applied Materials & Interfaces·Qiang LuoQiyong Gong

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.