Intracellular delivery is a critical step in biological discoveries and has been widely utilized in biomedical research. A variety of molecular tools have been developed for cell-based gene therapies, including FDA approved CAR-T immunotherapy, iPSC, cell reprogramming and gene editing. Despite the inspiring results of these applications, intracellular delivery of foreign molecules including nucleic acids and proteins remains challenging. Efficient yet non-invasive delivery of biomolecules in a high-throughput manner has thus long fascinates the scientific community. As one of the most popular non-viral technologies for cell transfection, electroporation has gone through enormous development with the assist of nanotechnology and microfabrication. Emergence of miniatured electroporation system brought up many merits over the weakness of traditional electroporation system, including precise dose control and high cell viability. These new generation of electroporation systems are of considerable importance to expand the biological applications of intracellular delivery, bypassing the potential safety issue of viral vectors. In this review, we will go over the recent progresses in the electroporation-based intracellular delivery and several potential applications of cutting-edge research on the miniatured electroporation, including gene therapy, cellular reprogramming and intracellular probe.

Background: Malignant brain tumor is a highly challenging disease for diagnosis, treatment, and management. Cytotoxicity, distribution and the ability to cross blood brain barrier are some of the most significant issues for the chemotherapy of brain tumors. Nanotechnology has been widely exploited in drug delivery with great potential in improving the drug efficiency and efficacy. The advent of nanotechnology would greatly facilitate the early detection and treatment of brain tumors. This review will be primarily focused on current nano drug delivery system for brain cancer therapy. Meanwhile, the existing impediments for therapeutic nanomedicines and critical analysis of the different delivery nanoparticles are also discussed. Methods: We systematically evaluated the major factors that impact the current nanomedicines for brain tumor therapy. Meanwhile, various nanoparticle-based formulations for brain cancer detection and therapy are evaluated. Results: 124 papers were included in this review. From the analysis of the nanomaterials, seven major nanomaterials have been discussed regarding the functionality and current therapeutic significance. The review also explains in detail about the different types of nanomaterials and their functionalities. This shows that each of these nanomaterials has specialized functions for the treatment of various kinds of brain cancer. Conclusion: Nanomaterials provide a viable potential diagnosis mechanis. In the future, more research needs to be focused on developing a better diagnosis tool for detection of cancer on an urgent basis. Blood-brain barrier and cytotoxicity are some of the primary root causes for the impediment of treatment of cancer using nanoparticles. Therefore, different delivery systems should be exploited for the nanoparticles to surmount these issues.

Background: Nanomedicine is an emerging therapeutic modality. Nanoparticles (NPs) are potential vehicles for delivery of anticancer therapeutics. NPs can be designed to facilitate tumor drug delivery both by passive and active targeting mechanisms. Passive targeting of NPs to tumors can be achieved through the enhanced permeability and retention (EPR) effect. Meanwhile, actively targeted NPs can be designed based on two different targeting mechanisms, ligand-directed targeting to the tumor cells and tumor microenvironment (TME)-directed targeting. Methods: We searched for and reviewed recently published literature on actively targeted NPs. Progress in this field was summarized in several focus areas, including methods for targeting of tumor cells and for targeting TME. Advantages and limitations of each approach were discussed. Results: This article covers data from 240 recent publications and provided numerous examples of ligand-directed NPs targeting tumor cell-selective surface receptors. Targeting ligands discussed include proteins such as transferrin and antibodies, as well as low molecular weight agents, such as peptides, aptamers, carbohydrates, and folate. In addition, extensive discussions of TME targeting NPs, designed to release drug in response to TME-specific stimuli, such as low pH, tumor-selective enzymes, and unique characteristics of tumor neovasculature, are also included in this review. In general, many novel actively targeting strategies have been developed and encouraging data have been reported in numerous settings, both in vitro and in animal studies. Conclusion: Active targeting of NPs has experienced rapid growth as a field of research and is continuously expanding. There are now some early examples of efforts on clinical translation and reported clinical trials on these NPs. Future development of actively targeted NPs depends on better understanding of the many factors affecting the behavior of NPs in vivo and likely involves combining the approaches of targeting the tumor cells and of targeting components of the TME.

Docetaxel (DTX) is an anticancer drug that is currently formulated with polysorbate 80 and ethanol (50:50, v/v) in clinical use. Unfortunately, this formulation causes hypersensitivity reactions, leading to severe side-effects, which have been primarily attributed to polysorbate 80. In this study, a DTX-loaded human serum albumin (HSA) nanoparticle (DTX-NP) was designed to overcome the hypersensitivity reactions that are induced by polysorbate 80. The methods of preparing the DTX-NPs have been optimized based on factors including the drug-to-HSA weight ratio, the duration of HSA incubation, and the choice of using a stabilizer. Synthesized DTX-NPs were characterized with regard to their particle diameters, drug loading capacities, and drug release kinetics. The morphology of the DTX-NPs was observed via scanning electron microscopy (SEM) and the successful preparation of DTX-NPs was confirmed via differential scanning calorimetry (DSC). The cytotoxicity and cellular uptake of DTX-NPs were investigated in the non-small cell lung cancer cell line A549 and the maximum tolerated dose (MTD) of DTX-NPs was evaluated via investigations with BALB/c mice. The study showed that the loading capacity and the encapsulation efficiency of DTX-NPs prepared under the optimal conditions was 11.2 wt% and 63.1 wt%, respectively and the mean diameter was less than 200 nm, resulting in higher permeability and controlled release. Similar cytotoxicity against A549 cells was exhibited by the DTX-NPs in comparison to DTX alone while higher maximum tolerated dose (MTD) with the DTX-NPs (75 mg/kg) than with DTX (30 mg/kg) was demonstrated in mice, suggesting that the DTX-NPs prepared with HSA yielded similar anti-tumor activity but were accompanied by less systemic toxicity than solvent formulated DTX. DTX-NPs warrant further investigation and are promising candidates for clinical applications.

Vitamin D₃ is an effective skin protective substance to prevent photoaging. Liposomes were used as a carrier to deliver vitamin D₃ to improve the stability and to enhance the treatment effect of vitamin D₃. The stability of vitamin D₃ liposomes, average cumulative penetration, and retention of vitamin D₃ in the skin were then evaluated and compared with free vitamin D₃. Finally, the treatment effect of vitamin D₃ liposomes in a rat photoaging model was appraised and Haematoxylin-Eosin (H&E) staining was used to assess the histology changes of the skin after vitamin D₃ liposome treatment. The results indicated that liposomes could significantly improve the stability of vitamin D₃. The average skin retention of vitamin D₃ liposomes was 1.65 times that of the vitamin D₃ solution. Vitamin D₃ liposomes could repair the surface morphology of skin in the photoaging model and promote the production of new collagen fibers. Vitamin D₃ liposomes as a potential skin care agent could significantly improve skin appearance and repair damage in the histology of photoaging.