摘要Nanomedicine has enormous potential in the diagnosis and treatment of malignant neoplasms.However,the clinical transla-tion of various nanoparticles(NPs)as drug delivery systems(DDSs)for tumor therapy remains poor.The main bottleneck is the limited database on the correlation between the design of NPs with unique physicochemical features and their therapeutic efficiency.In this study,we aim to design and investigate structurally variant nanocarriers composed of polylactide(PLA),silicon dioxide(SiO2),calcium carbonate(CaCO3),and barium carbonate(BaCO3)to reveal the relationship between their physicochemical features and therapeutic effectiveness against melanoma in vitro and in vivo.Specifically,we(1)examined their morphology,size,and structural characteristics;(2)evaluated colloidal stability;(3)verified the drug-loading and re-lease efficiency of a 2-aminothiophene scaffold(2AmT);(4)investigated cellular uptake and tumor spheroid penetration effi-ciency;(5)analyzed in vivo biodistribution;and(6)estimated therapeutic efficiency.The main characteristics of inorganic and organic NPs were collected and compared systematically.Considering the advantages and drawbacks of each NP type,the following tumor growth inhibition against melanoma was observed:CaCO3(87.9%-93.4%for 0.4 g/kg of 2AmT)>SiO2(75.6%-93.2%for 0.4 g/kg of 2AmT)>PLA(80.3%-88.2%for 0.4 g/kg of 2AmT)>BaCO3(58.8%-83.7%for 0.4 g/kg of 2AmT).Thus,this study contributes to the development of fundamental nanomedicine and accelerates the clinical translation of nanocarriers for effective melanoma therapy.