The suitable size of multifunctional nanomedicines strongly influences their physicochemical properties and actions in biological systems, for example, prolonged blood circulation time, efficient
tumor accumulation, and deep
tumor penetration. However, it is still a great challenge to construct size-transformable nanoparticles (NPs) for both efficient accumulation and penetration throughout
tumor tissue. Herein, a size-transformed multifunctional NP is developed through a simple bicomponent assembling strategy for enhanced
tumor penetration and efficient photo-chemo combined antitumor
therapy, due to the acidic tumor microenvironment and near infrared-
laser irradiation induced size-shrink. This multifunctional bicomponent NP (PP NP) driven by electrostatic interaction is composed of negatively charged
peptide amphiphile (PA1) and positively charged
peptide prodrug (PA2). PP NPs (≈170 nm) have been proven to improve blood circulation time and stability in biological environments. Interestingly, PP NPs can reassemble small NPs (<30 nm) by responding to acidic tumor microenvironment and near-infrared
laser irradiation, which facilitates deep
tumor penetration and improves cellular internalization. By integrating fluorescence imaging,
tumor targeting, deep
tumor penetration, and combined photo-
chemotherapy, PP NPs exhibit excellent in vivo antitumor efficacy. This study might provide an insight for developing a bicomponent assembling system with efficient
tumor penetration and multimode for antitumor
therapy.