Gene delivery as a promising and valid tool has been used for treating many serious diseases that conventional drug therapies cannot cure. Due to the advancement of physical technology and nanotechnology, advanced physical gene delivery methods such as electroporation, magnetoporation, sonoporation and optoporation have been extensively developed and are receiving increasing attention, which have the advantages of briefness and nontoxicity. This review introduces the technique detail of membrane perforation, with a brief discussion for future development, with special emphasis on nanoparticles mediated optoporation that have developed as an new alternative transfection technique in the last two decades. In particular, the advanced physical approaches development and new technology are highlighted, which intends to stimulate rapid advancement of perforation techniques, develop new delivery strategies and accelerate application of these techniques in clinic.

Since photodynamic therapy (PDT) has many advantages such as its minimally invasive procedure, low morbidity, minimum functional disturbance, good tolerance, ability to be used repeatedly at the same site, and the fact that it is largely an outpatient therapy,^1,2 it is a promising treatment modality for cancers and other malignant diseases.

Red blood cells (RBCs) have recently emerged as promosing candidates for cancer treatment in terms of relieving tumor hypoxia and inducing oxidative damage against cancer cells, but they are still far from satisfactory due to their limited oxygen transport and reactive oxygen species generation rate in tumor tissue. Herein, artificial RBCs (designated FTP@RBCM) with radical storm production ability were developed for oncotherapy through multidimensional reactivity pathways of Fe-protoporphyrin-based hybrid metal–organic frameworks (FTPs, as the core), including photodynamic/chemodynamic-like, catalase-like and glutathione peroxidase-like activities. Meanwhile, owing to the advantages of long circulation abilities of RBCs provided by their cell membranes (RBCMs), FTP with a surface coated with RBCMs (FTP@RBCM) could enormously accumulate at tumor site to achieve remarkably enhanced therapeutic efficiency. Intriguingly, this ROS-mediated dynamic therapy was demonstrated to induce acute local inflammation and high immunogenic cancer death, which evoked a systemic antitumor immune response when combined with the newly identified T cell immunoglobulin and mucin-containing molecule 3 (Tim-3) checkpoint blockade, leading to not only effective elimination of primary tumors but also an abscopal effect of growth suppression of distant tumors. Therefore, such RBC-mimic nanocatalysts with multidimensional catalytic capacities might provide a promising new insight into synergistic cancer treatment.

Purpose: As a promising photodynamic therapy (PDT) agent, Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS₄) provides deep penetration into tissue, high quantum yields, good photostability, and low photobleaching. However, its low delivery efficiency and high binding affinity to serum albumin cause its low penetration into cancer cells, further limiting its PDT effect on gastric cancer. In order to improve AlPcS₄/PDT effect, the AlPcS₄ delivery sys­tems with different drug carriers were synthesized and investigated. Materials and methods: Gold nanorods, cationic liposomes, and Pluronic^® F127 nanomicellars were used to formulate the AlPcS₄ delivery systems. The anticancer effect was evaluated by CCK-8 assay and colony formation assay. The delivery efficiency of AlPcS₄ and the binding affinity to serum proteins were determined by fluorescence intensity assay. The apoptosis and necrosis ability, reactive oxygen species and singlet oxygen generation, mitochondrial transmembrane potential and ([Ca²⁺]_i) concentration were further measured to evaluate the mechanism of cell death. Results: The series of synthesized AlPcS₄ delivery sys­tems with different drug carriers improve the limited PDT effect in varying degrees. In contrast, AlPcS₄ complex with gold nanorods has significant anticancer effects because gold nanorods are not only suitable for AlPcS₄ delivery, but also exhibit enhanced singlet oxygen generation effect and photothermal effect to induce cell death directly. Moreover, AlPcS₄ complex with cationic liposomes shows the potent inhibition effect because of its optimal AlPcS₄ delivery efficiency and ability to block serum albumin. In addition, AlPcS₄ complex with Pluronic F127 exhibits infe­rior PDT effect but presents lower cytotoxicity, slower dissociation rate, and longer retention time of incorporated drugs; thus, F127–AlPcS₄ is used for prolonged gastric cancer therapy. Conclusion: The described AlPcS₄ drug delivery systems provide promising agents for gastric cancer therapy.