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The poor prognosis of triple-negative breast cancer (TNBC) is attributed largely to the lack of tumor-selective therapeutic modalities that effectively deliver lethal doses at the sites of metastatic disease. Tumor-selective drug delivery strategies that aim to improve uniformity in intratumoral drug microdistributions and to prolong exposure of these cancer cells to delivered therapeutics may improve therapeutic efficacy against established TNBC metastases. In this study, we present lipid carriers for selective (due to their nanometer size) tumor delivery, which are loaded with cisplatin and designed to exhibit the following properties when in the tumor interstitium: (1) interstitial drug release (for deeper tumor penetration of cisplatin) and/or (2) intratumoral/ interstitial adhesion of the carriers to tumors' extracellular matrix (ECM)not accompanied by cell internalizationfor delayed tumor clearance of carriers prolonging cancer cell exposure to the cisplatin being released. We show that on large multicellular spheroids, used as surrogates of avascular solid tumor regions, greater growth inhibition was strongly correlated with spatially more uniform drug concentrations (due to interstitial drug release) and with longer exposure to the released drug (i.e., higher time-integrated drug concentrations enabled by slow clearing of adhesive nanoparticles). Lipid nanoparticles with both the release and adhesion properties were the most effective, followed by nanoparticles with only the releasing property and then by nanoparticles with only the adhering property. In vivo, cisplatinloaded nanoparticles with releasing and/or adhering properties significantly inhibited the growth of spontaneous TNBC metastases compared to conventional liposomal cisplatin, and the efficacy of different property combinations followed the same trends as in spheroids. This study demonstrates the therapeutic potential of a general strategy to bypass treatment limitations of established TNBC metastases due to the lack of cell-targeting markers: aiming to optimize the temporal intratumoral drug microdistributions for more uniform and prolonged drug exposure.

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modification, environmental remediation, imaging, and sensing. Full realization of the potential of biopolymer microparticles will require methods for rigorous characterization of particle sizes, morphologies, and dynamics, so that researchers may correlate particle characteristics with synthesis methods and desired functions. Toward this end, we evaluated biopolymer microparticles using dynamic imaging particle analysis, also known as flow imaging. This technology is becoming more widely used in the biopharmaceutical industry but is not yet well-known among the biomaterials community. Our polymer, a genetically engineered elastin-like polypeptide (ELP), self-assembles into micron-and submicron-scale coacervates. We performed flow imaging of ELP coacervates using two different instruments, one with a lower size limit of approximately 2 microns, the other with a lower size limit of approximately 300 nanometers. We validated flow imaging results by comparison with dynamic light scattering and atomic force microscopy analyses. We explored the effects of various solvent conditions on ELP coacervate size, morphology, and behavior, such as the dispersion of single particles versus aggregates. We found that flow imaging is a superior tool for thorough and statistically powerful particle analysis of ELP assemblies in solution. We anticipate that researchers studying many types of microscale protein or polymer assemblies will be interested in flow imaging as a tool for rapid, quantitative, solutionbased characterization.