Biodegradable Imprinted Polymer Based on ZIF-8/DOX-HA for Synergistically Targeting Prostate Cancer Cells and Controlled Drug Release with Multiple Responses

Abstract

Improving the drug loading and delivery efficiency of biodegradable nanomaterials used for targeting prostate cancer (PCa) remains a challenging task. To accomplish this task, herein, a new surface molecularly imprinted polymer (ZIF-8/DOX-HA@MIP) was designed and constructed with a hyaluronic acid (HA)-modified zeolitic imidazolate framework-8 (ZIF-8) metal–organic framework loaded with doxorubicin (DOX) as a substrate and a responsive molecularly imprinted polymer film as a shell. Owing to the large surface area of ZIF-8, DOX was successfully loaded into the ZIF-8/DOX-HA@MIP with a high drug loading efficiency (more than 88%). In vitro cell experiments have shown that the strengthened targeting ability of ZIF-8/DOX-HA@MIP to PCa cells was realized through the synergistic effect of HA and the molecularly imprinted membrane. Under the condition of simulated tumor microenvironment solution, Zn species were released and the particle size of ZIF-8/DOX-HA@MIP decreased gradually by the synergistic effect of hyaluronidase, pH, and glutathione, showing excellent biodegradability. In vivo antitumor research indicated the excellent antitumor activity and biocompatibility of ZIF-8/DOX-HA@MIP. The multifunctional ZIF-8/DOX-HA@MIP constructed herein provides a novel impetus for the development of targeted drug delivery in PCa treatment and a new strategy for treating other tumors.

Oxygen-carrying acid-responsive Cu/ZIF-8 for photodynamic antibacterial therapy against cariogenic Streptococcus mutans infection

“…This decrease is attributed to the plentiful negatively charged carboxyl groups of HA, which have a coordinating effect with the Zn 2+ in the material, thus neutralizing some of the positive charges and leading to a decrease in potential. 29–31 All of the above results indicate the successful preliminary synthesis of the nanomaterials.…”

Metal–Organic Frameworks-Based Nanoplatform for Treatment of Breast Cancer

“…The peaks at 870 and 805 cm –1 have corresponded to another two N–H characteristic DOX peaks. Those results indicated the successful preparation of DZZ NPs with core–shell structure, large surface areas, and improved drug loading capacity. − …”

Hyaluronic Acid-Conjugated Fluorescent Probe-Shielded Polydopamine Nanomedicines for Targeted Imaging and Chemotherapy of Bladder Cancer

“…The cells incubated with HR-PDD NPs exhibited stronger DOX fluorescence than that of PDD NPs at 2 and 6 h. Fluorescence quantitative analysis using ImageJ software showed that the DOX fluorescence in the cells treated with HR-PDD NPs was 1.28 times higher as compared to that in the cells treated with PDD NPs at 6 h (Figure B). The significantly enhanced DOX fluorescence mainly benefited from the interaction between HA and the CD44 receptor. , HA bound the CD44 receptor overexpressed on tumor cells and facilitated the cell uptake of HR-PDD NPs. Next, we further examined the cellular internalization and subsequent DOX release profiles using flow cytometry (Figure C).…”