Enhance Cancer Cell Recognition and Overcome Drug Resistance Using Hyaluronic Acid and α-Tocopheryl Succinate Based Multifunctional Nanoparticles.
Mol Pharm. 2015 May 6;
Authors: Liang S, Wang AT, Yang ZZ, Liu YJ, Qi XR
Multidrug resistance (MDR) presents a clinical obstacle to cancer chemotherapy. The main purpose of this study was to evaluate the potential of a hyaluronic acid (HA) and α-tocopheryl succinate (α-TOS) based nanoparticle to enhance cancer cell recognition and overcome MDR, and to explore the underlying mechanisms. A multifunctional nanoparticle, HTTP-50 NP, consisted of HA-α-TOS (HT) conjugate and D-α-tocopheryl polyethylene glycol succinate (TPGS) with docetaxel loaded in its hydrophobic core. The promoted tumor cell recognition and accumulation, cytotocicity, mitochondria-specific apoptotic pathways for the HTTP-50 NP were confirmed in MCF-7/Adr cells (P-gp-overexpressing cancer model), indicating that the formulated DTX and the conjugated α-TOS in the HTTP-50 NP could synergistically circumvent the acquired and intrinsic MDR in MCF-7/Adr cells. In vivo investigation on the MCF-7/Adr xenografted nude mice models confirmed that HTTP-50 NP possessed much higher tumor tissue accumulation and exhibited pronouncedly enhanced anti-resistance tumor efficacy with reduced systemic toxicity compared with HTTP-0 NP and Taxotere. The mechanisms of the multifunctional HTTP-50 NP to overcome MDR and enhance anti-resistance efficacy may be contributed by CD44 receptor-targeted delivery, P-gp efflux inhibition, and meanwhile to maximize antitumor efficacy by synergism of DTX and mitocan of α-TOS killing tumor cells.
PMID: 25945733 [PubMed – as supplied by publisher]