Calixarene‐Embedded Nanoparticles for Interference‐Free Gene–Drug Combination Cancer Therapy

Abstract

Combination therapy based on molecular drugs and therapeutic genes provides an effective strategy for malignant tumor treatment. However, effective gene and drug combinations for cancer treatment are limited by the widespread antagonism between therapeutic genes and molecular drugs. Herein, a calixarene‐embedded nanoparticle (CENP) is developed to co‐deliver molecular drugs and therapeutic genes without compromising their biological functions, thereby achieving interference‐free gene–drug combination cancer therapy. CENP is composed of a cationic polyplex core and an acid‐responsive polymer shell, allowing CENP loading and delivering therapeutic genes with improved circulation stability and enhanced tumor accumulation. Moreover, the introduction of carboxylated azocalix[4]arene, which is a hypoxia‐responsive calixarene derivatives, in the polyplex core endows CENP with the capability to load molecular drugs through the host–guest complexation as well as inhibit the interference between the drugs and genes by encapsulating the drugs into its cavity. By loading doxorubicin and a plasmid DNA‐based CRISPR interference system that targets miR‐21, CENP exhibits the significantly enhanced anti‐tumor effects in mice. Considering the wide variety of calixarene derivatives, CENP can be adapted to deliver almost any combination of drugs and genes, providing the potential as a universal platform for the development of interference‐free gene–drug combination cancer therapy.

Spatial Distribution Control of Antimicrobial Peptides through a Novel Polymeric Carrier for Safe and Efficient Cancer Treatment

“…PCA was synthesized as previously reported. [21] PKLA 3 -co-PPBE 6 was synthesized by the copolymerization of a norbornenyl group modified phenylboronic ester and a norbornenyl group modified KLA (Table S1, Supporting Information) via ringopening metathesis polymerization (ROMP) using a Grubbs 3rd initiator. [22] For comparison, PKLA 3 (without the hydrophobic block) and a non-ROS-responsive copolymer, PKLA 3 -co-PPhe 9 (Phe stands for benzene ring), was synthesized similarly (Figure S9 and Table S2, Supporting Information).…”

Nanotherapeutics Overcoming the Blood-Brain Barrier for Glioblastoma Treatment

“…In the presence of Cas9 (a bacterially derived enzyme that snips DNA) and a synthetic guide RNA, CRISPR work as a RNA-guided gene-editing platform to introduce a double-strand break at a specific location within the genome. The delivery of CRISPR/Cas9 and genes is also a novel antitumor strategy to overcome tumor heterogeneity ( Liu et al, 2019a ; Liu et al, 2021b ).…”

Role of Calixarene in Chemotherapy Delivery Strategies

“…The complex reduces the interference between drug and gene, improving stability and selectivity towards the therapeutic target. The observed anticancer effect is better in mice treated with the calixarene-DOX-DNA plasmid complex [ 61 ].…”