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The efficacy of chemotherapeutic drugs in tumor treatment is limited by their toxicity and side effects due to their inability to selectively accumulate in tumor tissue. In addition, chemotherapeutic agents are easily pumped out of tumor cells, resulting in their inadequate accumulation. To overcome these challenges, a drug delivery system utilizing the amphiphilic peptide Pep1 was designed. Pep1 can self-assemble into spherical nanoparticles (PL/Pep1) and encapsulate paclitaxel (PTX) and lapatinib (LAP). PL/Pep1 transformed into nanofibers in an acidic environment, resulting in longer drug retention and higher drug concentrations within tumor cells. Ultimately, PL/Pep1 inhibited tumor angiogenesis and enhanced tumor cell apoptosis. The use of shape-changing peptides as drug carriers to enhance cancer cell apoptosis is promising. [Display omitted] • The drug-loaded peptide PL/Pep1 self-assembled to form spherical nanoparticles. • PL/Pep1 underwent a morphological transformation to prolong the retention of the encapsulated drugs. • PL/Pep1 inhibited tumor angiogenesis and enhanced tumor cell apoptosis. [ABSTRACT FROM AUTHOR]

[Display omitted] • The acidic tumor microenvironment induced a geometrical shape change by amphiphilic peptide LKR nanoparticles. • The obtained targeted LKR nanoparticles were simple but effective with no modification. • Anticancer drugs can be loaded and encapsulated into LKR nanoparticles with no covalent crosslinking. • LKR nanoparticles enhanced the drug accumulation in tumor cells compared with normal mammalian cells. • LKR was used in combination with encapsulated drugs for antitumor therapy in vivo. Spatial accuracy is crucial in drug delivery, especially to increase the efficacy and reduce the side effects of antitumor drugs. In this study, we developed a simple and broadly applicable strategy in which a target peptide ligand was introduced to construct a pH-responsive drug-loading system to achieve targeted delivery and drug release in lesions. In addition to reaching the tumor tissue through passive targeting modalities such as the enhanced permeability and retention (EPR) effect, active targeting nanoparticles used RGD motifs coupled to nanocarriers to specifically bind certain integrins, such as α ν β3, which is expressed on the surface of tumor cells, to achieve active tumor cell targeting. Self-assembling peptides have significant advantages in their structural design. The amphiphilic peptide LKR could form a spherical and self-assembled nanoparticle, which encapsulated the fat-soluble antitumor drug doxorubicin (Dox) in neutral medium. The Dox-encapsulating peptide nanoparticles swelled and burst, rapidly releasing Dox in an acidic microenvironment. Flow cytometry and fluorescence detection showed that the self-assembled LKR nanoparticles enhanced the drug accumulation in tumor cells compared with normal mammalian cells. The Dox-encapsulating peptide nanoparticles exhibited desirable antitumor effects in vivo. In summary, the acidic microenvironment of tumors was used to induce drug release from a targeted peptide drug-loading system to enhance cellular uptake and therapeutic effects in situ , providing a promising therapeutic approach for the treatment of major diseases such as hepatoma. [ABSTRACT FROM AUTHOR]

• pH triggered a geometrical shape switch by I 6 K 5 nanoparticles. • The obtained I 6 K 5 nanoparticles were simple but smart with no modification. • Anticancer drugs can be loaded and encapsulated into I 6 K 5 nanoparticles. • Tumor cells took in more I 6 K 5 nanoparticles than mammalian cells. • This system gives new insights in the field of cancer therapeutic platforms. The geometry of nanoparticles plays an important role in their performance as drug carriers. However, the pH-triggered geometrical shape switching of a cationic peptide consisting of isoleucine and lysine is seldom reported. In this work, we designed a cationic peptide with acid reactivity that can be loaded with the poorly soluble antitumor drug (doxorubicin (DOX)) to enhance tumor cell uptake and drug delivery. In a weakly acidic environment, a large portion of random coil structures formed, which subsequently led to nanoparticle destruction and rapid DOX release. In vitro studies demonstrated that this cationic peptide exhibits low toxicity to normal cells. The amount of DOX-encapsulating peptide nanoparticles taken up by tumor cells was greater than that taken up by normal cells. Our results indicated that the use of a weakly acidic microenvironment to induce geometric shape switching in drug-loaded peptide nanoparticles should be a promising strategy for antitumor drug delivery. [ABSTRACT FROM AUTHOR]