Polypeptide-Based Theranostics with Tumor-Microenvironment-Activatable Cascade Reaction for Chemo-ferroptosis Combination Therapy

Abstract

Nanoengineering of polymer-based therapeutic carriers is promising for precise cancer treatment. Herein, we report the fabrication of polypeptide vehicles encapsulated with anticancer drug of cisplatin (Pt drug) and Fe 3 O 4 nanoparticles (denoted as Pt&Fe 3 O 4 @PP) as theranostics for T 2 -weighted magnetic resonance imaging (MRI)-guided chemo-ferroptosis combination therapy. The number of Fe 3 O 4 nanoparticles per polypeptide vehicle is well controlled by adjusting the added amount of Fe 3 O 4 nanoparticles. The tumor microenvironment can trigger the release of Pt drug and Fe 2/3+ , which could induce the intracellular cascade reaction to generate sufficient • OH for ferroptosis therapy. Moreover, the released Pt drug can cause the apoptosis of tumor cells. Meanwhile, the encapsulated Fe 3 O 4 nanoparticles can also be used for T 2weighted MRI of tumor. Both in vitro and in vivo results indicate that the reported Pt&Fe 3 O 4 @PP can efficiently inhibit cancer cell growth without causing significant systemic toxicity. Importantly, polypeptide vehicles could significantly reduce the side effect of free Pt drug in vivo and therefore improve the drug delivery efficacy. Our findings suggest that polypeptide-based theranostics with tumor-microenvironment-activatable cascade reaction have great potential in biomedical applications.

Carrier-free nanodrugs for safe and effective cancer treatment

“…As shown in Fig. 2a, generally, one or multiple types of clinical drug molecules are dissolved in a small amount of organic solvent and then added dropwisely into an aqueous solution under vigorous stirring [68]. Due to the interactions between the hydrophobic small molecules, uniform nanoparticles are rapidly obtained [69].…”

The synthesis of a nanodrug using metal-based nanozymes conjugated with ginsenoside Rg3 for pancreatic cancer therapy

“…Fe ions are barely released at neutral pH, but sufficient release is achieved via acid hydrolysis in the TME. 43,44 Rg3 are more effectively degraded and transformed under acidic conditions than in neutral environments. 32 When Fe ions and Rg3 are hydrolyzed or degraded under acidic conditions, separation of the NPs and the organic pharmaceutical ingredients results.…”

Nanoparticulation of Prodrug into Medicines for Cancer Therapy

“…carboxyl-modified Fe 3 O 4 NPs and positively charged poly(Llysine) through electrostatic interaction, Gao et al constructed a polypeptide-based nano-vehicle which fulfilled the combined antitumor treatment by released Pt drug and generated sufficient • OH, meanwhile used for T 2 -weighted MRI of tumor. [224] CA4 represents a critical vascular disrupting strategy for tumor therapy, but the anti-polymerization effect of CA4 on tubulin is reversible and its rapid biological clearance has compromised its overall therapeutic efficiency. To fully potentialize CA4, Liu et al proposed a poly(l-glutamic acid)-CA4 conjugate(PLG-CA4) prodrug nanomedicine which resulted in a 74% tumor suppression rate while commercial CA4 phosphate only showed 24%, attributing to the PLG-CA4 being largely spread around the tumor vessels (Figure 15A).…”