pH-responsive high stability polymeric nanoparticles for targeted delivery of anticancer therapeutics

• Published in: Communications biology Vol. 3; no. 1; p. 95
• Main Authors: Palanikumar, L., Al-Hosani, Sumaya, Kalmouni, Mona, Nguyen, Vanessa P., Ali, Liaqat, Pasricha, Renu, Barrera, Francisco N., Magzoub, Mazin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.03.2020
• Subjects: 101/28; 101/58; 13/106; 13/2; 13/31; 14/19; 14/33; 14/34; 14/63; 631/154/152; 631/1647/350/354; 631/61/350/354; 631/92/152; 64/60; 692/699/67/1059/602; Acids - pharmacology; Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacokinetics; Biomedical and Life Sciences; Cell Line, Tumor; Cell Proliferation - drug effects; Doxorubicin - administration & dosage; Doxorubicin - pharmacokinetics; Doxorubicin - pharmacology; Drug Carriers - chemical synthesis; Drug Carriers - chemistry; Drug Carriers - therapeutic use; Drug Compounding; Drug Delivery Systems - methods; Drug Liberation - drug effects; Drug Stability; Female; HeLa Cells; Humans; Hydrogen-Ion Concentration; Life Sciences; MCF-7 Cells; Mice; Mice, Inbred C3H; Nanoparticles - chemistry; Nanoparticles - therapeutic use; Peptide Fragments - chemistry; Peptide Fragments - drug effects; Polylactic Acid-Polyglycolic Acid Copolymer - chemistry; Serum Albumin, Bovine - chemistry; THP-1 Cells; Xenograft Model Antitumor Assays
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-020-0817-4

The practical application of nanoparticles (NPs) as chemotherapeutic drug delivery systems is often hampered by issues such as poor circulation stability and targeting inefficiency. Here, we have utilized a simple approach to prepare biocompatible and biodegradable pH-responsive hybrid NPs that overcome these issues. The NPs consist of a drug-loaded polylactic-co-glycolic acid (PLGA) core covalently ‘wrapped’ with a crosslinked bovine serum albumin (BSA) shell designed to minimize interactions with serum proteins and macrophages that inhibit target recognition. The shell is functionalized with the acidity-triggered rational membrane (ATRAM) peptide to facilitate internalization specifically into cancer cells within the acidic tumor microenvironment. Following uptake, the unique intracellular conditions of cancer cells degrade the NPs, thereby releasing the chemotherapeutic cargo. The drug-loaded NPs showed potent anticancer activity in vitro and in vivo while exhibiting no toxicity to healthy tissue. Our results demonstrate that the ATRAM-BSA-PLGA NPs are a promising targeted cancer drug delivery platform. Palanikumar et al. prepare pH-responsive nanoparticles with drug-loaded PLGA core, cross-linked BSA corona to avoid opsonisation, and functionalised with ATRAM peptide that binds the cell membrane at low pH such as tumour microenvironment. The nanoparticles display both in vitro and in vivo efficacy while evading recognition by macrophages.