Nanoparticles can be enriched at tumor site and improve the therapeutic efficacy of many chemother- apy drugs with the well-known enhanced permeability and retention （EPR） effect. While conventional preparations of materials for nanoscale drug delivery system mainly focused on chemical synthesis, recently the combination of synthetic carrier and natural biomimetic carrier has gained more and more attention. As a new generation of biomimetic nanoparticles, cell membrane-coated nanoparticles combine the complex biological functions of natural membranes and the physicochemical properties of synthetic nanomaterials for a more effective drug delivery. Herein, we briefly review the recent advances on cell membrane-coated nanoparticles for tumor-targeted drug delivery via the prolonging systemic circulation lifetime and the active targeting effect. Since the preferential accumulation of cell membrane-coated nanopar- ticles in tumor site, they are able to improve the therapeutic efficacy of conventional chemotherapy drugs in antitumor treatment as well as to reduce the systemic toxicity. We also introduce a systematic targeted strategy for the promising application of this platform on brain tumors.
Chemotherapies for brain diseases have been hampered due to the inability of transport of drug across the blood-brain barrier (BBB). In order to overcome the barrier, p-hydroxybenzoic acid (p-HA), a small molecule of benzamide analogue, was used as a ligand for brain-targeted drug delivery. The p-HA was conjugated to PEG-DSPE to form p-HA-PEG-DSPE. Docetaxel-loaded polymeric micelles were prepared by a thin-film hydration method using methoxy-poly(ethylene glycol)-distearoylphosphatidyl- ethanolamine (mPEG 2000 -DSPE) as a carrier and the p-HA-PEG-DSPE as a brain targeted material. The prepared micelles showed spherical with a mean diameter of (18±3) nm. Encapsulation efficiency and drug loading were (83.49±1.3)%, (7.7±1.2)% for un- modified micelles and (80.65±1.6)%, (7.47±1.8)% for p-HA-modified micelles, respectively. In vitro cellular uptake experiments showed that the p-HA-modified micelles increased BCECs cellular uptake by 1.2 times compared to the unmodified micelles. Ex vivo near-infrared fluorescence imaging showed that brain uptake of the p-HA-modified micelles was 1.3-1.8 times higher than that of the unmodified micelles. In vitro cytotoxicity assay against glioblastoma cell U87 MG showed that inhibition rate of the p-HA-modified micelles increased by 1.2 times compared to that of the unmodified micelles and 1.7 times compared to that of DTX. Survival time of nude mice bearing intracranial glioblastoma showed that the lifetime of saline group, Taxotere group, mPEG-DSPE/DTX micelles group and p-HA-PEG-DSPE/DTX micelles group was 22, 27, 32 and 45.8 d, representively, which indicated that anti-glioblastoma activity of DTX could be significantly enhanced by the p-HA-modified polymeric micelles. These results demonstrated that the p-HA-modified micelles could be a promising brain-targeted drug delivery system for hydrophobic drugs against glioblastoma.
In order to deliver and/or release anti-cancer therapeutics at the tumor sites, novel environment-responsive drug delivery systems are designed to specifically respond to tumor microenvironment （such as low pH and hypoxia）. Due to their extraordinary advantages, these environment-responsive drug delivery systems can improve antitumor efficacy, and most importantly, they can decrease toxicity associated with the anti-cancer therapeutics. This review highlights different mechanisms of environmentresponsive drug delivery systems and their applications for targeted cancer therapy.
Despite the application of aggressive surgery,radiotherapy and chemotherapy in clinics,brain tumors are still a difficult health challenge due to their fast development and poor prognosis.Brain tumor-targeted drug delivery systems,which increase drug accumulation in the tumor region and reduce toxicity in normal brain and peripheral tissue,are a promising new approach to brain tumor treatments.Since brain tumors exhibit many distinctive characteristics relative to tumors growing in peripheral tissues,potential targets based on continuously changing vascular characteristics and the microenvironment can be utilized to facilitate effective brain tumor-targeted drug delivery.In this review,we briefly describe the physiological characteristics of brain tumors,including blood–brain/brain tumor barriers,the tumor microenvironment,and tumor stem cells.We also review targeted delivery strategies and introduce a systematic targeted drug delivery strategy to overcome the challenges.
