Intracellular delivery is considered an indispensable process for various studies, ranging from medical applications (cell-based therapy) to fundamental (genome-editing) and industrial (biomanufacture) approaches. Conventional macroscale delivery systems critically suffer from such issues as low cell viability, cytotoxicity, and inconsistent material delivery, which have opened up an interest in the development of more efficient intracellular delivery systems. In line with the advances in microfluidics and nanotechnology, intracellular delivery based on micro- and nanoengineered platforms has progressed rapidly and held great promises owing to their unique features. These approaches have been advanced to introduce a smorgasbord of diverse cargoes into various cell types with the maximum efficiency and the highest precision. This review differentiates macro-, micro-, and nanoengineered approaches for intracellular delivery. The macroengineered delivery platforms are first summarized and then each method is categorized based on whether it employs a carrier- or membrane-disruption-mediated mechanism to load cargoes inside the cells. Second, particular emphasis is placed on the micro- and nanoengineered advances in the delivery of biomolecules inside the cells. Furthermore, the applications and challenges of the established and emerging delivery approaches are summarized. The topic is concluded by evaluating the future perspective of intracellular delivery toward the micro- and nanoengineered approaches.
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http://dx.doi.org/10.1002/adma.202005363 | DOI Listing |
Adv Healthc Mater
January 2025
State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, 541004, China.
Despite the significant potential of short hairpin RNA (shRNA)-mediated gene therapy for various diseases, the clinical success of cancer treatment remains poor, partly because of low selectivity and low efficiency. In this study, an mRNA-initiated autonomous multi-shRNA nanofactory (RNF@CM) is designed for in vivo amplification imaging and precise cancer treatment. The RNF@CM consists of a gold nanoparticle core, an interlayer of two types of three-stranded DNA/RNA hybrid probes, one of which is bound to aptamer-inhibited DNA polymerases, and an outer layer of the cancer cell membrane.
View Article and Find Full Text PDFJ Control Release
January 2025
Centre de Biophysique Moléculaire, CBM, CNRS UPR4301, Orléans, France. Electronic address:
The development of lipid-based mRNA delivery systems has significantly facilitated recent advances in mRNA-based therapeutics. Liposomes, as the pioneering class of mRNA vectors, continue to lead in clinical trials. We previously developed a histidylated liposome that demonstrated efficient nucleic acid delivery.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
University of Science and Technology of China, Department of Polymer Science and Engineering, 96 Jinzhai Road, 230026, , 230026, Hefei, CHINA.
Understanding the interplay between gasotransmitters is essential for unlocking their therapeutic potential. However, achieving spatiotemporally controlled co-delivery to target cells remains a significant challenge. Herein, we propose an innovative strategy for the intracellular co-delivery of carbon monoxide (CO) and nitric oxide (NO) gasotransmitters under clinically relevant wavelengths.
View Article and Find Full Text PDFAnalyst
January 2025
Department of Engineering Design, Indian Institute of Technology Madras, India.
High throughput intracellular delivery of biological macromolecules is crucial for cell engineering, gene expression, therapeutics, diagnostics, and clinical studies; however, most existing techniques are either contact-based or have throughput limitations. Herein, we report a light-activated, contactless, high throughput photoporation method for highly efficient and viable cell transfection of more than a million cells within a minute. We fabricated reduced graphene oxide (rGO) nanoflakes that was mixed with a polydimethylsiloxane (PDMS) nanocomposite thin sheet with an area of 3 cm and a thickness of ∼600 μm.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
Department of Pharmaceutics, Ghent University, 9000 Ghent, Belgium.
The intracellular delivery of peptides and proteins is crucial for various biomedical applications. Lipid nanoparticles (LNPs) have emerged as a promising strategy for delivering peptides to phagocytic cells. However, the diverse physicochemical properties of peptides necessitate tailored formulations.
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