recognize and bind to tumor-associated antigens such as CD19 and epidermal growth factor receptor (EGFR) before releasing cytotoxic granules and effector cytokines to destroy cancer cells. [3] CAR-T therapy has shown remarkable success against CD19 expressing B cell hematological malignancies and, thus far, five products (Kymriah from Novartis; Yescarta and Tecartus from Kite Pharma/Gilead Sciences; and Breyanzi and Abecma from Bristol-Myers Squibb) have been approved by the US Food and Drug Administration (FDA) for clinical use. [4,5] Currently, there are at least 500 clinical trials registered on ClinicalTrials.gov database using engineered immune cells to treat various cancers including that of the brain, lungs, and skin.Despite the clinical success of CAR-T cells against B cell leukemia, CAR-T therapy still face tremendous challenges in manufacturing, safety, and affordability before it can become a viable clinical option. [6] One of the biggest technical difficulties is to transfect sensitive, primary T cells whereby biomolecules like oligonucleotides and proteins have to be delivered intracellularly and into the nuclei of cells. FDA-approved gold standard viruses and bulk electroporation suffer from low transfection efficiency while also perturbing the critical biological attributes of cells such as proliferation, metabolism, and gene expression. [7] This increases the time and costs for cell expansion, and without an efficient and cost-friendly transfection technology, the price (between USD 0.4-0.5 million per patient) for FDA-approved CAR treatments (Kymriah and Yescarta) will remain unaffordable and untimely. [8] The limitations in conventional transfection techniques have motivated the development of micro-and nanoplatforms such as microfluidics, nanoparticles, and high-aspect-ratio nanostructures to improve immune cell viability and throughput during transfection.Herein, we first provide an overview of CAR-T cell manufacturing, with emphasis on the science of transfection and limitations of traditional technology using viruses and bulk electroporation. There will also be discussion of other cell-based cancer immunotherapy using other types of promising immune cell types. Next, we describe emerging transfection platforms and companies that have been established to overcome gaps in CAR-T transfection. We then provide a list of assays constituting the polyfunctionalities of immune cells that we believe will help the field better assess the robustness and suitability of their transfection methods. Finally, we end off with existing challenges in CAR-T transfection and how overcoming these challenges can significantly enhance the clinical impact of CAR-T therapy.Chimeric antigen receptor T cell (CAR-T) therapy holds great promise for preventing and treating deadly diseases such as cancer. However, it remains challenging to transfect and engineer primary immune cells for clinical cell manufacturing. Conventional tools using viral vectors and bulk electroporation suffer from low efficiency while posing risks ...

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Cellular senescence refers to a state of irreversible arrest of cell proliferation in response to various forms of cellular stress. It is known that the accumulation of senescent cells is a hallmark of aging, and mounting evidence has shown that the chronic accumulation of senescent cells is a significant contributor to various deleterious age-related pathologies. To limit the detrimental impacts of cellular senescence, there has been growing interest in targeted delivery of therapeutics to senescent cells to treat age-related pathologies and promote healthy aging. Two popular strategies include the elimination of senescent cells using senolytic drugs, and rejuvenation of senescent cells. To that end, it is integral that the delivery of senolytics, senomorphics or rejuvenating biomolecules to senescent cells are highly selective to enhance delivery efficacy and safety. However, there is little understanding of how senescence-associated biophysical changes such as cellular size and stiffness can be exploited for targeted therapeutics delivery. In this review, the biomolecular and biophysical markers of senescence along with senescence models and emerging therapeutics are first described. This review then focuses on how biophysical properties can be exploited for targeted therapeutics delivery, using approaches like nanoparticles, electroporation, sonoporation, photoporation and high aspect-ratio nanostructures to senescent cells.

The authors have examined seven reasonable asymmetrical dimer configurations for a Si(100) surface using the CNDO method. In this work, all structures resulting from higher-order dimer reconstruction are named according to Pauling and Herman's terminology. Reconstructed 4*1 and 4*2 surfaces are found to be energetically more favourable, followed by 2*2A and 2*1. The total energies per dimer of these four structures are reasonably close to each other and a disordered mixture of them might appear at the Si(100) surface. The results agree well with previous theoretical work as well as with experimental results. However, the 4*1 configuration cannot be confirmed as it has not been observed experimentally. The results on the amount of charge transfer to the dimer atoms and the dimer lengths for each configurations are also presented.

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