Combinatorial Polydopamine-Liposome Nanoformulation as an Effective Anti-Breast Cancer Therapy

Abstract

Introduction Drug delivery systems (DDSs) based on liposomes are potential tools to minimize the side effects and substantially enhance the therapeutic efficacy of chemotherapy. However, it is challenging to achieve biosafe, accurate, and efficient cancer therapy of liposomes with single function or single mechanism. To solve this problem, we designed a multifunctional and multimechanism nanoplatform based on polydopamine (PDA)-coated liposomes for accurate and efficient combinatorial cancer therapy of chemotherapy and laser-induced PDT/PTT. Methods ICG and DOX were co-incorporated in polyethylene glycol modified liposomes, which were further coated with PDA by a facile two-step method to construct PDA-liposome nanoparticles (PDA@Lipo/DOX/ICG). The safety of nanocarriers was investigated on normal HEK-293 cells, and the cellular uptake, intracellular ROS production capacity, and combinatorial treatment effect of the nanoparticles were assessed on human breast cancer cells MDA-MB-231. In vivo biodistribution, thermal imaging, biosafety assessment, and combination therapy effects were estimated based on MDA-MB-231 subcutaneous tumor model. Results Compared with DOX·HCl and Lipo/DOX/ICG, PDA@Lipo/DOX/ICG showed higher toxicity on MDA-MB-231 cells. After endocytosis by target cells, PDA@Lipo/DOX/ICG produced a large amount of ROS for PDT by 808 nm laser irradiation, and the cell inhibition rate of combination therapy reached up to 80.4%. After the tail vein injection (DOX equivalent of 2.5 mg/kg) in mice bearing MDA-MB-231 tumors, PDA@Lipo/DOX/ICG significantly accumulated at the tumor site at 24 h post injection. After 808 nm laser irradiation (1.0 W/cm 2 , 2 min) at this timepoint, PDA@Lipo/DOX/ICG efficiently suppressed the proliferation of MDA-MB-231 cell and even thoroughly ablated tumors. Negligible cardiotoxicity and no treatment-induced side effects were observed. Conclusion PDA@Lipo/DOX/ICG is a multifunctional nanoplatform based on PDA-coated liposomes for accurate and efficient combinatorial cancer therapy of chemotherapy and laser-induced PDT/PTT.

Targeted Co-Delivery of FOXM1 Aptamer and DOX By Nucleolin Aptamer-Functionalized pH-Responsive Biocompatible Nanodelivery System to Enhance Therapeutic Efficacy Against Breast Cancer: In Vitro and In Vivo

“…The cardiomyocytes histoarchitecture in AF-PDA-DOX@TNP group was similar to normal cardiac tissue [23].…”

Polydopamine-Modified Liposomes: Preparation and Recent Applications in the Biomedical Field

“…This behavior has been ascribed to a possible decomposition of the polymeric layer in acidic conditions, but this topic is still under debate. Finally, the release of drugs from PDA-coated liposomes was stimulated by NIR radiation, likely due to the heat generated by the photothermal effect …”

“…The strategies proposed to obtain a PDA coating on the surface of isolated liposomes are quite simple and generally follow the same scheme. Commonly, the strong templating effect of liposomes is exploited by simply inducing the in situ polymerization of DA in a liposomal suspension in TRIS buffer at pH 8.5 ,,,, or phosphate buffer at pH 8.0 (Figure B). , In fact, it has been observed that to ensure a good PDA coating, it is important that the anchoring takes place at an early stage of the polymerization process or, better, that the polymerization is performed in the presence of the vesicles to be coated. Indeed, when the PDA particles are already formed, the majority of uncyclized aminoethyl groups have already converted to indoles, which are less prone to adhesion .…”

Recent Advances in Nanomaterials-Based Targeted Drug Delivery for Preclinical Cancer Diagnosis and Therapeutics

“…Additionally, liposomal nanoformulation of DOX and ICG was done through their PEGylation and further coated with polydopamine (PDA), which resulted in the formation of PDA@Lipo/DOX/ICG nanoparticle. This nanoparticle was reported to exhibit remarkable anti-cancer therapeutic efficacy after being subjected to irradiation for PDT [34]. Lipid nanoparticles (LNPs) have also emerged as one of the most cutting-edge methods for the effective in vivo administration of exogenous mRNA vaccine.…”