Layer-by-layer pH-sensitive nanoparticles for drug delivery and controlled release with improved therapeutic efficacy in vivo

Abstract

In this work, a pH-sensitive liposome-polymer nanoparticle (NP) composed of lipid, hyaluronic acid (HA) and poly(b-amino ester) (PBAE) was prepared using layer-by-layer (LbL) method for doxorubicin (DOX) targeted delivery and controlled release to enhance the cancer treatment efficacy. The NP with pH-sensitivity and targeting effect was successfully prepared by validation of charge reversal and increase of hydrodynamic diameter after each deposition of functional layer. We further showed the DOX-loaded NP had higher drug loading capacity, suitable particle size, spherical morphology, good uniformity, and high serum stability for drug delivery. We confirmed that the drug release profile was triggered by low pH with sustained release manner in vitro. Confocal microscopy research demonstrated that the NP was able to effectively target and deliver DOX into human non-small cell lung carcinoma (A549) cells in comparison to free DOX. Moreover, the blank NP showed negligible cytotoxicity, and the DOX-loaded NP could efficiently induce the apoptosis of A549 cells as well as free DOX. Notably, in vivo experiment results showed that the DOX-loaded NPs effectively inhibited the growth of tumor, enhanced the survival of tumor-bearing mice and improved the therapeutic efficacy with reduced side-effect comparing with free drug. Therefore, the NP could be a potential intelligent anticancer drug delivery carrier for cancer chemotherapy, and the LbL method might be a useful strategy to prepare multi-functional platform for drug delivery.

Nanoparticle Surface Functionalization: How to Improve Biocompatibility and Cellular Internalization

“…Furthermore, the NPs surface was modified with hyaluronic acid (HA) to perform active targeting via CD44. In vivo experiments confirmed the results obtained in vitro, showing that the DOX-loaded NPs inhibited the growth of tumor more efficiently compared to free drug and also reduced side-effects (Men et al, 2020). Another example of pH-sensitive NPs is reported by Taleb et al (2019).…”

Dye‐Loaded Nanoemulsions: Biomimetic Fluorescent Nanocarriers for Bioimaging and Nanomedicine

“…Moreover, change in the pH can induce disassembly of the NEs and therefore pH-controlled cargo release. [110]…”

Multi-Smart and Scalable Bioligands-Free Nanomedical Platform for Intratumorally Targeted Tambjamine Delivery, a Difficult to Administrate Highly Cytotoxic Drug

“…One example is the development of nanoparticles with a large structure to avoid blood clearance that shrink once pH decreases in tumor, enhancing cell penetration [ 14 ]. Another study describes the synthesis of nanosystems that are chemically stable under physiological conditions but release the encapsulated drug when pH conditions become acidic, showing an improved tolerability in blood [ 15 ].…”