Background: The development of biocompatible tumor-targeting delivery systems for
anticancer agents is essential for efficacious cancer chemotherapy. Nanoparticles, as drug delivery
cargoes for cancer therapy, are rapidly improving to overcome the limitations of conventional chemotherapeutic
agents. Heparin–modified nanoparticles are currently being considered as one of the
favorable carriers for the delivery of chemotherapeutics to cancer tissues.
Objective: This study was aimed at evaluating the in vitro and in vivo antitumor activity of a novel
targeted, pH-sensitive, heparin-based polymeric micelle loaded with the poorly water-soluble anticancer
drug, docetaxel (DTX). The micelles could overcome the limited water solubility, non-specific
distribution, and insufficient drug concentration in tumor tissues.
Methods: DTX-loaded folate targeted micelles were prepared and evaluated for physicochemical
properties, drug release, in vitro cellular uptake and cytotoxicity in folate receptor-positive and folate
receptor-negative cells. Furthermore, the antitumor activity of DTX-loaded micelles was evaluated
in the tumor-bearing mice. Some related patents were also studied in this research.
Results: The heparin-based targeted micelles exhibited higher in vitro cellular uptake and cytotoxicity
against folate receptor over-expressed cells due to the specific receptor-mediated endocytosis.
DTX-loaded micelles displayed greater antitumor activity, higher anti-angiogenesis effects, and
lower systemic toxicity compared with free DTX in a tumor-induced mice model as confirmed by
tumor growth monitoring, immunohistochemical evaluation, and body weight shift. DTX-loaded
targeting micelles demonstrated no considerable toxicity on major organs of tumor-bearing mice
compared with free DTX.
Conclusion: Our results indicated that DTX-loaded multifunctional heparin-based micelles with desirable
antitumor activity and low toxicity possess great potential as a targeted drug delivery system
in the treatment of cancer.