Vinblastine-Loaded Nanoparticles with Enhanced Tumor-Targeting Efficiency and Decreasing Toxicity: Developed by One-Step Molecular Imprinting Process

Abstract

Molecularly imprinted polymers have exhibited good performance as carriers on drug loading and sustained release. In this paper, vinblastine (VBL)-loaded polymeric nanoparticles (VBL–NPs) were prepared by a one-step molecular imprinting process, avoiding the waste and incomplete removal of the template, and evaluated as targeting carriers for VBL delivery after modification. Using acryloyl amino acid comonomers and disulfide cross-linkers, VBL–NPs were synthesized and then conjugated with poly­(ethylene glycol)–folate. The dynamic size of the obtained VBL–NPs–PEG–FA was 258.3 nm (PDI = 0.250), and the encapsulation efficiency was 45.82 ± 1.45%. The nanoparticles of VBL–NPs–PEG–FA were able to completely release VBL during 48 h under a mimic tumor intracellular condition (pH 4.5, 10 mM glutathione (GSH)), displaying significant redox responsiveness, whereas the release rates were much slower in the mimic body liquid (pH 7.4, 2 μM GSH) and tumor extracellular environment (pH 6.5, 2 μM GSH). Furthermore, the carriers NPs–PEG–FA, prepared without VBL, showed satisfactory intrinsic hemocompatibility, cellular compatibility, and tumor-targeting properties: they could rapidly and efficiently accumulate to folate receptor positive Hela cells and then internalized via receptor-mediated endocytosis, and the retention in tumor tissues could last for over 48 h. Interestingly, VBL–NPs–PEG–FA could evidently increase the accumulation of VBL in tumor tissues while decreasing the distribution of VBL in organs, exert similar anticancer efficacy against Hela tumors in the xenograft model of nude mice to VBL injection, and significantly improve the abnormality of liver and spleen observed in VBL injection. VBL–NPs–PEG–FA has the potential to be the delivery carrier for VBL by enhancing the tumor-targeting efficacy of VBL and decreasing toxicity to normal tissues.

Molecularly Imprinted Polymers in Biological Applications

“…The MIPs were loaded with a drug sensitive to high concentrations of glutathione (an environment that can be found in cancer cells), to target and treat tumors in vivo in mice [181]. Combining targeting folate-positive cancer cells with loading the MIPs with the glutathione-sensitive drug vinblastine showed that the drug accumulated in tumor tissues while the drug concentration decreased in organs, as compared with the pure drug, decreasing the toxicity of the drug to healthy tissues [182].…”

Sialic Acid as a Biomarker Studied in Breast Cancer Cell Lines In Vitro Using Fluorescent Molecularly Imprinted Polymers

“…Cancer cells use several mechanisms to bypass recognition by the immune cells, thereby escaping immune surveillance and progressing through metastases [4]. The cir-Appl.…”

Advances in Molecularly Imprinted Polymers as Drug Delivery Systems

“…Therefore, MIPs with a lower degree of cross-linking are usually more advantageous for applications in drug delivery. Furthermore, the introduction of external materials such as thermosensitive polymers [70], magnetite [71] and specific moieties such as disulphide bonds [72] allows to MIPs to exhibit suitable changes in response to external stimuli, such as changes in pressure, pH, temperature, ionic strength, electric fields, chemicals and light.…”