Nanoporous electroporation needle for localized intracellular delivery in deep tissues

Abstract

The exogenous control of intracellular drug delivery has been shown to improve the overall efficacy of therapies by reducing nonspecific off-target toxicity. However, achieving a precise on-demand dosage of a drug in deep tissues with minimal damage is still a challenge. In this study, we report an electric-pulse-driven nanoporeelectroporation (nEP) system for the localized intracellular delivery of a model agent in deep tissues. Compared with conventional bulk electroporation, in vitro nEP achieved better transfection efficiency (>60%) with a high cell recovery rate (>95%) under a nontoxic low electroporation condition (40 V). Furthermore, in vivo nEP using a nanopore needle electrode with a side drug-releasing compartment offered better control over the dosage release, time, and location of propidium iodide, which was used as a model agent for intracellular delivery. In a pilot study using experimental animals, the nEP system exhibited two times higher transfection efficiency of propidium iodide in the thigh muscle tissue, while minimizing tissue damage (<20%) compared to that of bulk electroporation. This tissue-penetrating nEP platform can provide localized, safe, and effective intracellular delivery of diverse therapeutics into deep tissues in a controlled manner.

Advanced technologies for biomedical applications by emerging researchers in Asia‐Pacific

“…5 The electric-pulse-driven nanopore-electroporation system using the needle electrode was developed by Lee et al, which enables the precise and targeted intracellular delivery of small molecules into deep tissues. 6 Luo et al incorporated tannic acid, a naturally derived antimicrobial agent, into electrospun polyvinyl alcohol fibers for the healing of infected wounds. 7 Yang et al fabricated the peroxide-derived AgAu-based nanoboxes to treat Clostridioides difficile infection.…”

“…Yoo et al prepared the thiamine pyrophosphate‐decorated human serum albumin nanoclusters adsorbing doxorubicin or methotrexate to achieve the synergistic anti‐tumor effects with cisplatin for osteosarcoma therapy 5 . The electric‐pulse‐driven nanopore‐electroporation system using the needle electrode was developed by Lee et al, which enables the precise and targeted intracellular delivery of small molecules into deep tissues 6 . Luo et al incorporated tannic acid, a naturally derived antimicrobial agent, into electrospun polyvinyl alcohol fibers for the healing of infected wounds 7 .…”

Liver‐tumor mimics as a potential translational framework for planning and testing irreversible electroporation with multiple electrodes

“…Yet for early diagnoses, partial liver resection is suitable for only 5%–10% of patients with a small (<2 cm) nonmetastatic disease from which half of them recur within 2 years after surgery 3 . Next to liver surgery, numerous ablation therapies have come to light as curative alternatives and as a means of sustainability of hepatic tissue, for example, radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation, localized drug delivery with electrochemotherapy (ECT), and irreversible electroporation (IRE) 1,4,5 . At present, RFA is the most used ablation therapy in HCC treatment, showing a local recurrence up to 31%.…”

“… 3 Next to liver surgery, numerous ablation therapies have come to light as curative alternatives and as a means of sustainability of hepatic tissue, for example, radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation, localized drug delivery with electrochemotherapy (ECT), and irreversible electroporation (IRE). 1 , 4 , 5 At present, RFA is the most used ablation therapy in HCC treatment, showing a local recurrence up to 31%. Nonetheless, IRE is being increasingly preferred since it has reduced the local recurrence to 7.5% while lacking the heat‐sink effect.…”