Biodistribution of tumor-targeted MXene-antibody conjugates.

Abstract

The biodistribution profile is a critical determinant of the success of nanomaterial applications, governing both therapeutic efficacy and systemic safety in emerging photothermal therapy (PTT) agents. Despite the promise of PTT, the clinical translation of many nanomaterial-based photothermal agents is impeded by intrinsic toxicity and insufficient tumor specificity. Moreover, off-target biodistribution of photosensitizers after systemic administration can increase systemic exposure, reduce tumor delivery, and ultimately compromise therapeutic efficacy, underscoring the need for advanced material delivery concepts that enhance selective tumor accumulation and therapeutic outcome. Here, we present a targeted MXene-based PTT platform designed to address these challenges. Among the tested MXenes (Ti₃C₂, Nb₂C, and V₂C), Ti₃C₂ was identified as the most biocompatible and safest candidate, demonstrating minimal cytotoxicity, negligible impact on cell-cycle progression, and no significant impairment of long-term proliferative capacity. Ti₃C₂ MXene was subsequently coated with polydopamine (PDA) and conjugated to an anti-human-CEACAM1 (hCC1) antibody (Ab) to enable antigen-dependent tumor targeting. In a murine melanoma model bearing human CC1-positive (hCC1+) and CEACAM1-negative (hCC1-) tumors, we evaluated the outcomes of both intravenous (IV) and intratumoral (IT) administration of the Ti₃C₂-PDA-anti-hCC1 nanoconjugate. Quantification of titanium by inductively coupled plasma atomic emission spectrometry (ICP-AES), in combination with histological analysis, revealed preferential accumulation of the targeted nanoconjugate in hCC1+ tumors compared with hCC1- controls. Notably, after IV delivery, Ti₃C₂-PDA-anti-hCC1 conjugate demonstrated enhanced deposition in the tumor and lower non-specific uptake in clearance organs, including the liver, lungs, and spleen, compared with non-antibody-functionalized MXene. Collectively, these results support the Ti₃C₂-PDA-anti-hCC1 conjugates as a tumor-selective biodistribution platform with reduced clearance-organ burden, supporting further therapeutic validation of MXene-based targeted PTT.