A Cancer Cell Membrane‐Derived Biomimetic Nanocarrier for Synergistic Photothermal/Gene Therapy by Efficient Delivery of CRISPR/Cas9 and Gold Nanorods

Abstract

Bimodal synergistic therapy produces superadditive effect for enhanced therapeutic efficacy. However, how to efficiently and simultaneously deliver several kinds of therapeutic agents is still challenging. A cancer cell membrane‐derived nanocarrier (mCas9‐sGNRs) is proposed for synergistic photothermal/gene therapy (PTT/GT) by efficient delivery of clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR‐associated protein 9 (Cas9) and gold nanorods (GNRs). In this approach, Cas9 proteins can be efficiently loaded inside the cell membranes (mCas9) by electrostatic interactions. Similarly, single‐guide RNAs, which target survivin, can be loaded onto GNRs (sGNRs) through electrostatic interactions and encapsulated by mCas9. As a result, the nanodelivery systems present advantages in biocompatibility, homologous targeting capacity and loading efficiency of cargoes. In addition, significant antitumor effects is achieved by gene editing of survivin which induces anticancer activity and reduces heat tolerance of cancer cells caused by GNRs mediated PTT due to the downregulation of HSP70. These results indicate the nanotherapeutic platform leads to enhanced PTT/GT efficacy. Therefore, this work not only provides a general strategy to construct a versatile nanoplatform for loading and target delivery of several therapeutic cargos but will also be valuable for PTT/GT and other bimodal synergistic therapy.

Biogenic materials for CRISPR delivery and therapeutics

“…90 (F) Schematic illustration of the synthesis procedures of mCas9-sGNRs and the processes of combined PTT/gene therapy. 93 For example, liposomes were fused with exosomes to form hybrid exosomes, and successful encapsulation of dCas9-sgRNA expression vectors can double the delivery efficiency (Fig. 4C).…”

“…4F). 93 The CRISPR-Cas9 gene editing system for disease therapy is a very new approach and recent studies have reported their application in nanotechnology-based delivery and disease therapy using extracellular vesicles and vesicles derived from cell membranes. We believe that the development of nanoplatforms based on gene editing technology using cell association has promising applications in the field of delivery systems and disease treatment.…”

“…(E) Schematic illustration of the synthesis and application of biomimetic MOFs for ulcerative colitis (UC) treatment 90. (F) Schematic illustration of the synthesis procedures of mCas9-sGNRs and the processes of combined PTT/gene therapy 93.…”

Nanoengineering a Zeolitic Imidazolate Framework‐8 Capable of Manipulating Energy Metabolism against Cancer Chemo‐Phototherapy Resistance

“…Consequently, a low level of ATP restrained the expression of P-gp (Figure 3K), an efficient drug efflux transporter, to increase the sensitivity of MCF-7 Adr cells to DOX. In addition, ATP reduction also decreased the expression of heat shock protein 70 (HSP70) (Figure 3K), a stress response protein which defends against hyperthermia, [30] to enhance the efficiency of PTT. Unsurprisingly, our CS/NPs greatly promoted apoptosis ratios in both parental and drug-resistant MCF-7 cells compared with free DOX, A780, DOX+A780, and NPs (Figure 3L,M and Figure S4G,H, Supporting Information).…”

Natural Chlorogenic Acid Planted Nanohybrids with Steerable Hyperthermia for Osteosarcoma Suppression and Bone Regeneration

“…[27][28][29][30] Among them, gold nanorods have been widely used in promising drug delivery thanks to their large specific surface area and facile synthesis method. [31][32][33][34][35][36] Moreover, due to their tunable surface plasmon and photothermal effects, gold nanorods are extensively famous for generating hyperthermia (>50 °C) for tumor photothermal therapy (PTT) under a near-infrared (NIR) laser. [31,34,[36][37] Interestingly, recent research has been reported that a few photothermal agents including black phosphorus, AuPd alloy nanoparticles, and carbon nanotubes could produce mild localized heat (40-43 °C) for osteogenesis and mineralization.…”