Multifunctional siRNA-Laden Hybrid Nanoplatform for Noninvasive PA/IR Dual-Modal Imaging-Guided Enhanced Photogenetherapy

Abstract

Small interfering RNA (siRNA)-induced gene therapy has been recognized as a promising avenue for effective cancer treatment, while easy enzymatic degradation, poor transfection efficiency, nonspecific biodistribution, and uncontrolled release hinder its extensive clinical applications. Zeolitic imidazolate frameworks-8 (ZIF-8) have emerged as promising drug carriers without an in-depth exploration in programmable siRNA delivery. Herein, we report a multifunctional PDAs-ZIF-8 (PZ) nanoplatform for delivering siRNA with combined photothermal therapy (PTT) and gene therapy (GT) via the noninvasive guidance of photoacoustic (PA)/near-infrared (IR) dual-modal imaging. The ingenious PZ nanocarriers mediated the tumor-specific accumulation of therapeutic siRNA without undesired degradation and preleakage. The pH-responsive ZIF-8 decomposed in an acidic tumor microenvironment that was accompanied by the release of siRNA payloads for cleaving target mRNA in gene silencing therapy. Meanwhile, the polydopamine nanoparticles (PDAs) could simultaneously serve as a powerful noninvasive PA/IR imaging contrast agent and versatile photothermal agent for diagnosis-guided photogenetherapy. The systematic in vitro and in vivo experimental explorations demonstrated that our PDAs-siRNA-ZIF-8 (PSZ) could greatly enhance the therapeutic efficiency as compared with the corresponding PTT or GT monotherapy. This work holds great potential to advance the development of more intelligent diagnosis and therapeutic strategies, thus supplying promising smart nanomedicines in the near future.

Polydopamine‐Based Nanoparticles for Photothermal Therapy/Chemotherapy and their Synergistic Therapy with Autophagy Inhibitor to Promote Antitumor Treatment

“…PDA, assembled by oxidative self‐polymerization of dopamine monomer, also incorporates abundant functional groups (such as amine, imine, and catechol) [26] . Consequently, PDA has the following extraordinary features: (1) negatively potential in a neutral or slightly alkaline environment, resulting in good stability; (2) a strong ligand of multivalent metals (such as manganese, [34] iron, [35] and copper ions [36] ), which enables imaging function; (3) reacting with many groups (such as sulfhydryl group or amino group) to form a covalent bond, which makes PDA easily to be further modified; [37,38] (4) exhibiting the striking property of strong adhesion to almost all substrates, which adhesive to the metal surface by forming a reversible noncovalent bond and to the organic residue by an irreversible covalent bond; [39] (5) abundant π electron clouds of PDA for high loading ability with other molecules containing π systems (such as drugs [40,41] and siRNA [42] ).…”

The Biology and Function of Extracellular Vesicles in Cancer Development

“…SiRNAs are produced by short, exogenous double-stranded RNAs (dsRNAs) as an RNA interference (RNAi) tool (Kim et al, 2018;Dharamdasani et al, 2020;Feng et al, 2020). SiRNA can be used to effectively silence target genes.…”

Progress in Delivery of siRNA-Based Therapeutics Employing Nano-Vehicles for Treatment of Prostate Cancer

“…There are a number of differences between miRs and siRNAs. The first difference is that miRs are formed endogenously from non-coding RNAs, while siRNAs are produced by exogenous long double-stranded RNAs (dsRNAs) [ 53 , 54 ]. The transportation of miRs during their biogenesis on the route of the nucleus to the cytoplasm is performed via importin 8 (IPO-8).…”