Electroporation-Enhanced Delivery of Bleomycin for Cancer Therapy: An Investigative Study Spanning In Vitro, In Vivo, and Clinical Trials

Electrochemotherapy (ECT) is an emerging, clinically applied method combining cytotoxic drugs (like bleomycin) with local electroporation – the application of electric fields to transiently increase cell membrane permeability [1]. This significantly enhances intracellular drug uptake, particularly for poorly permeating agents like bleomycin, increasing local effectiveness dramatically. ECT is internationally approved and used for both curative and palliative purposes, most effectively for small, superficial lesions [2]. It can improve quality of life by reducing pain, bleeding, preserving function, and offering cosmetic benefits, even achieving remission in selected cases. A key advantage is its predominantly local effect, making it potentially applicable in patients with organ dysfunction, as administered drug concentrations can be lower [3]. Here, we present preclinical (in vitro and in vivo) experiments and a clinical case study demonstrating the efficacy of intracellular bleomycin electrotransfer for cutaneous metastatic melanoma. In vitro studies: Chinese hamster ovary (CHO) and murine breast cancer (4T1) cells were used. Electroporation parameters 1 pulse 1000 – 1800 V/cm, 1 Hz, 100µs and bleomycin concentrations were from 5 to 20 nM. Cell viability after treatment was assessed using colony formation assays. In vivo studies: Female BALB/c mice were inoculated with 4T1 cells to induce tumors. Once tumors were established, mice were treated with intravenous bleomycin followed by electrical pulses applied directly to the tumor area according to the ESOPE protocol. Tumor volume was measured daily to monitor treatment response. Clinical Case Study: A 68-year-old male with extensively pre-treated, progressive cutaneous metastatic melanoma was treated with palliative ECT. The primary goal was symptom control and quality of life improvement. Preclinical findings (in vitro and in vivo) demonstrate the efficacy of bleomycin electrotransfer in tumour cell killing and tumor growth control. A clinical case study illustrates that ECT can be a valuable palliative option for patients with superficial melanoma metastases when conventional treatments are exhausted. It offers good local control, symptomatic relief, and is well tolerated, making it a relevant therapeutic consideration even in advanced disease stages.