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In the development of drug delivery system (DDS)-based anticancer drugs, the techniques for the intratumor mapping and quantification of active pharmaceutical ingredients (API) in pharmaceuticals must be pivotal for predicting pharmacological effects and adverse events. X-ray fluorescence spectrometry (XRF) is a potent analytical tool for mapping/quantifying platinum pharmaceutics such as oxaliplatin (l-OHP) and its liposomal formulation. In recent studies, we employed XRF to visualize the intratumor micro-distribution of l-OHP in a tumor-bearing model mouse intravenously injected with either free l-OHP or l-OHP liposomes. The intratumor distribution of l-OHP within tumor sections could be determined by XRF to detect platinum atoms. After treatment with the liposomal formulation, the l-OHP was localized near the tumor vessels and, via repeated injections, increasingly accumulated in tumors by a much greater degree than treatment with free l-OHP. The repeated injections of l-OHP liposomes improved the vascular permeability via inducing the apoptosis of tumor cells near the tumor vessels, which should improve the tumor microenvironment and enhance the intratumor accumulation of repeated doses of l-OHP liposomes. The proposed process was also used to visualize the intratumor distribution of l-OHP in rectal cancer specimens resected from a patient who had received l-OHP-based preoperative chemotherapy. We further revealed that neutralization of an acidic tumor microenvironment via oral administration with NaHCO 3 could improve the therapeutic efficacy of weakly basic anticancer agent-encapsulating liposomes. Collectively, mapping/quantifying the intratumor API in DDS drugs and/or improving the tumor microenvironment would be an effective means to accelerate the clinical development of DDS-based anticancer drugs.

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Elucidation for Intratumor Localization of a DDS-based Anticancer Drug and Enhancement of Its Therapeutic Effects <i>via</i> Improvement of the Tumor Microenvironment

Elucidation for Intratumor Localization of a DDS-based Anticancer Drug and Enhancement of Its Therapeutic Effects via Improvement of the Tumor Microenvironment