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The invention covers a lysosomal membrane protein SLC46A3 that acts as a nanoparticle-specific biomarker for informing cancer cell affinity for liposomal nanoparticles. This discovery was derived from a high-throughput pooled screen of hundreds of cancer cell lines against 40 nanoparticle and antibody formulations - low SLC46A3 expression showed strong association with high liposomal nanoparticle uptake. This inverse relationship is consistent across multiple cancer cell types and lineages as well as liposomal nano-formulations, thus establishing SLC46A3 expression as a cancer-agnostic biomarker. This relationship was validated in vivo via intravenous and intratumoral injection of a liposomal nanoparticle formulation using an engineered melanoma mouse model. Notably, in patient tumor data, cancer cells expressing low levels of SLC46A3 are associated with aggressive tumor phenotypes and poor prognosis. Therefore, strategic integration of this biomarker into patient cohort selection during clinical trials could potentially minimize non-uniform biological response to nanoparticles, thereby providing a more uniform clinical readout of the investigational drug.