M29 - Micro Implantable Cisplatin Synthesis (Mics) Device for in-situ Chemotherapy

Introduction: : Cisplatin is a cornerstone chemotherapeutic agent for treating a range of solid tumors, yet patients often experience severe systemic toxicity and poor tumor specificity [1]. It is attributed to the fact that conventional intravenous delivery exposes healthy organs to off-target effects, resulting in nephrotoxicity, neurotoxicity, and acquired resistance [2]. In this abstract, we introduce a Micro Implantable Cisplatin Synthesis (MICS) device (Fig. 1), a system that can synthesize cisplatin in situ by recapitulating the first cisplatin discovery, i.e., a combination of electrochemical and photochemical mechanisms.
The proposed MICS integrates a UV LED and platinum electrode array, orchestrated by an ultra-small microcontroller. This setup enables autonomous synthesis directly from endogenous fluids without the need for drug reservoirs. Notably, the microcontroller-enabled programmability enables site-specific activation of cisplatin production, minimizing systemic exposure while maximizing local therapeutic potency [3–5]. The MICS represents a disruptive shift in chemotherapy delivery, transforming cisplatin from a systemically administered drug into a precision-targeted, on-demand therapeutic.

Materials and

Methods: : Fig. 2 shows the system architecture of the proposed MICS device. The ultra-small microcontroller (ATtiny10-TSHR) was programmed to generate a pulse-width modulation (PWM) signal with 200 ms ON and 100 ms OFF cycles for performing electrolysis via platinum electrodes and a UV LED (395 nm). The device was powered using a 5V DC supply delivered through a 2-pin, 4 mm magnetic connector, which can be easily attached for operation. During operation, the device consumes 8.9 mA of current.
The printed circuit board (PCB) was designed and fabricated on a flexible copper-clad polyimide sheet (Dupont) using a UV laser machine (Full Spectrum). The flexible PCB could be folded up to three times during assembly, reducing the PCB size significantly. With all assembled components (including 5 mm long platinum wire) and passivation, the prototype size was 15 mm in length and 5 mm in width.
To confirm cisplatin synthesis, UV–Vis absorption spectra were collected after 60 minutes of pulsed electrolysis (200 ms ON / 100 ms OFF at 6V) and UV LED treatment. We also validated the cytotoxicity of the MICS-synthesized cisplatin using in vitro cytotoxicity testing using U251 glioblastoma cells; four different treatment conditions were designed: UV only, electrolysis only, MICS, and clinical cisplatin (6.6 µM).

Results, Conclusions, and Discussions:: Fig. 3a shows the UV-VIS spectra of the MICS-generated compound, which exhibited a strong peak at 301 nm, a cisplatin signature, compared to the clinical-grade cisplatin. It is noted that the MICS-synthesized cisplatin may contain some impurity, which requires assessing the toxicity.
Fig. 3b summarizes the results. UV and electrolysis alone reduced cell viability to 82.6% and 44.1%, respectively. In contrast, the MICS-treated glioblastoma cells showed a significant reduction in cell viability of 26.0%, demonstrating a greater cytotoxic effect than standalone methods and approaching the potency of free cisplatin (50.0%). Control and sham groups maintained >95% viability, confirming minimal off-target effects.
These results highlight the efficacy of MICS as a programmable, minimally invasive implantable microdevice for localized cisplatin synthesis and delivery. Compact, flexible design is expected to support repeated treatments with reduced systemic toxicity. This platform presents a novel direction for next-generation chemotherapeutic implants,

Acknowledgements and/or References (Optional):: [1] Wheate, N. J., et al. Dalton Transactions, 2010, 39, 8113.
[2] Johnstone, T. C., et al. Chemical Reviews, 2016, 116, 3436.
[3] Campbell, R., et al. Advanced Healthcare Materials, 2021, 10, 2001582.
[4] Wang, Z., et al. Journal of The Electrochemical Society, 2014, 161, F380.
[5] Reedijk, J., et al. Pharmaceutical Weekblad Scientific Edition, 1985, 7, 173.