Abstract
Improving the efficacy of nanoparticles (NPs) delivery to tumors is critical for cancer diagnosis and therapy. In our previous work, amphiphilic peptide APPA self-assembled nanocarriers were designed and constructed for cargo delivery to tumors with high efficiency. In this study, we explore the use of APPA self-assembled peptosomes as a nanoparticle adjuvant to enhance the delivery of nanoparticles and antibodies to integrin αvβ3 and neuropilin-1 (NRP1) positive tumors. The enhanced tumor delivery of coadministered NPs was confirmed by better magnetosome (Mag)-based T2-weighted magnetic resonance imaging (MRI), liposome-based fluorescence imaging, as well as the improved anti-tumor efficacy of monoclonal antibodies (trastuzumab in this case) and doxorubicin (DOX)-containing liposomes. Interestingly, the improvement is most significant for the delivering of compounds that have active or passive tumor targeting ability, such as antibodies or NPs that have enhanced permeability and retention (EPR) effect. However, for non-targeting small molecules, the effect is not significant. In vitro and in vivo studies suggest that both peptosomes and the coadministered compounds might be internalized into cells through a NRP1 mediated co-endocytosis (CoE) pathway. The improved delivery of coadministered NPs and antibodies to tumors suggests that the coadministration with APPA self-assembled peptosomes could be a valuable approach for advancing αvβ3 and NRP1 positive tumors diagnosis and therapy.
Highlights
Nanocarriers loaded with drugs and probes are expected to improve tumor diagnosis and treatment while reducing the side effects
The in vitro tumor penetration efficacy of LipoDOX coadministered with PADiR peptosomes was studied using a multicellular tumor spheroid (MCTS) model
To study the therapeutic efficacy of trastuzumab coadministered with amphiphilic peptide PA (APPA) self-assembled peptosome on mice bearing 4T1-H orthotopic tumors, the 4T1 cell line was transfected with pMH3-HER2 vector to construct the HER2 high expressing cell line (4T1-H)
Summary
Nanocarriers loaded with drugs and probes are expected to improve tumor diagnosis and treatment while reducing the side effects. An alternative solution is using a simple compound as an adjuvant to assist the nanocarriers delivering to tumors One example of such a compound is the iRGD (CRGDKGPDC) peptide [12,13], which contains a consensus R/KXXR/K motif (CendR motif) and becomes active after being proteolytically cleaved at the tumor site [14]. We further demonstrate that the APPA self-assembled peptosomes can be used as an adjuvant to improve the delivery of antibodies, nanoprobes, and nanodrugs to tumors We suggest that such a coadministration strategy can be a straightforward and effective approach for clinical cancer diagnosis and therapy
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