Homotypic Targeting Delivery of siRNA with Artificial Cancer Cells

Abstract

The camouflage with cell membrane bestows nanoparticles with cell‐like functions, such as specific recognition, long blood circulation, and immune escaping. For cancer therapy, the nanoparticles camouflaged with cancer cell membrane (CCM) from homologous cells show homotypic targeting delivery of small molecule compounds, photosensitizers, or enzymes to the tumors. However, effective gene therapy encounters difficulties by this approach due to the properties of nucleic acids. Herein, a cancer cell‐like gene delivery system is developed using an excellent polymer poly(β‐amino ester) (PBAE) to condense small interfering RNA (siRNA) (targeting to Plk1 gene) into nanoparticles (PBAE/siPlk1) as the core, which is further camouflaged with CCM. These novel biomimetic nanoparticles CCM/PBAE/siPlk1 (CCMPP) demonstrate highly specific targeting to homotypic cancer cells, effective downregulation of PLK1 level, and inducing apoptosis of cancer cells. Based on the homotypic binding adhesion molecules on the CCM, the cellular internalization and homotypic‐targeting accumulation to the tumors are clearly improved. CCMPP induces highly efficient apoptosis of cancer cells both in vitro and in vivo and results in significant tumor inhibition. The artificial cancer cells with homotypic properties can serve as a biomimetic delivery system for cancer‐targeted gene therapy.

A Novel Biomimetic Nanoprobe as a Photoacoustic Contrast Agent

“…The phenomenon is attributed to some reasons: 1) the absolute value of MPD was ∼25 mV, about 10 mV higher than that of PD; 2) the camouflage with cell membranes lowered the surface energy; and 3) the camouflage with cell membranes reduced the aggregation or non-specific adsorption. The characteristics were also confirmed by the previous work (Zhang et al, 2020b). Furthermore, we measured the DiR loading capacities with increasing DiR concentrations (Figure 1E).…”

“…Recently, biomimetic functionalization engineering NPs have shown superior biocompatibility and smart targeting to desired tissues ( Zhang et al, 2020a ; Peng et al, 2021 ). Specifically, biomimetic NPs with cell membrane coating manifest cell-material hybrid nanoplatforms that combine the advantages of both natural and synthetic elements ( Kroll et al, 2017 ; Zhang et al, 2020b ). Biomimetic NPs own special functions because they have the protein of the source cells, such as ligand recognition and targeting ( Chen et al, 2020 ), immune escaping ( Hu et al, 2011 ), and long blood circulation ( Gao et al, 2017 ).…”

Design of polymers for siRNA delivery: Recent progress and challenges

“…For example, cancer cell membrane-coated biomimetic nanoparticles could specifically delivery siRNA to homologous tumors in vivo (Figure 10A). [240,241] One of the challenges for cell membrane-decorated polyplexes is how to release the cargo siRNAs from coated membranes after endocytosis. To solve this issue, charge-reversal polymers with negative surface charges at physiological pH were proposed to disrupt the lipid bilayers by converting the polymers to positively charged ones under acidic conditions.…”

Efficient Photoacoustic Imaging With Biomimetic Mesoporous Silica-Based Nanoparticles

“…Cell membrane coating is widely used to fabricate biomimetic nanoparticles, which has been considered as a promising approach for precise tumor diagnosis and treatment ( Fang et al, 2018 ; Zhang L. et al, 2020 ; Zhang Y. et al, 2020 ; Li et al, 2020 ). Various cell types, including red blood cells (RBC) ( Dehaini et al, 2017 ; Kim et al, 2020 ), platelets ( Dehaini et al, 2017 ; Kunde and Wairkar, 2021 ), white blood cells ( Yaman et al, 2020 ), cancer cells ( Yang et al, 2018 ) and stem cells ( Defterali et al, 2016 ), have been coated with the nanoparticles ( Fang et al, 2018 ).…”

“…In comparison with polymer coating, cell membranes coated with nanoparticles exhibited low immunogenicity and excellent homologous targeting ability ( Fang et al, 2018 ; Li et al, 2020 ; Lin et al, 2021 ; Peng et al, 2021 ). For cancer diagnosis and treatment, based on the homologous targeting ability, nanoparticles coated with the cancer cell membrane from homologous cells could efficiently deliver drugs and probes to the tumors ( Fang et al, 2018 ; Zhang L. et al, 2020 ). Therefore, MSNs fabricated with the cancer cell membrane from the homologous Hela cells might efficiently deliver ICG to the cervical tumor and significantly enhance the PA imaging for cervical cancer via the homologous targeting ability.…”