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Systemic Administration with Bacteria-Inspired Nanosystems for Targeted Oncolytic Therapy and Antitumor
Cheng Shen1, Yachao Li1,2, Zenan Zeng1
1Department of Pharmacy, College of Biology, Hunan University, Changsha, Hunan 410082, China.
Abstract:
Malignant tumors represent a formidable global health challenge, compelling the pursuit of innovative treatment modalities. Oncolytic therapy has emerged as a promising frontier in antitumor strategies. However, both natural agents (such as oncolytic bacteria or viruses) and synthetic oncolytic peptides confront formidable obstacles in clinical trials, which include the delicate equilibrium between safety and efficacy, the imperative for systemic administration with targeted therapy, and the need to counteract oncolysis-induced immunosuppression. To overcome these dilemmas, we have developed biomimetic nanoengineering to create oncolytic bacteria-inspired nanosystems (OBNs), spanning from hierarchical structural biomimicry to advanced bioactive biomimicry. Our OBNs harbor inherent oncolytic potential, including functionalized oligosaccharides mimicking bacterial cell walls for optimal blood circulation and tumor targeting, tumor acidity-switchable decoration for tumor-specific oncolysis, stereospecific tryptophan-rich peptides for robust oncolytic activity, encapsulated tumor immunomodulators for enhanced immunotherapy, and innate multimodal imaging potential for biological tracing. This work elucidates the efficacy and mechanisms of OBNs, encompassing primary tumor suppression, metastasis prevention, and recurrence inhibition. Systemic administration of d-chiral OBNs has demonstrated superior oncolytic efficacy, surpassing intratumoral injections of clinical-grade oncolytic peptides. This work heralds an era in biomimetic engineering on oncolytic agents, promising the revolutionization of contemporary oncolytic therapy paradigms for clinical translation.
Insights
Biomimetic nanoengineering created oncolytic bacteria-inspired nanosystems (OBNs) for cancer therapy. These OBNs show superior efficacy in tumor suppression, metastasis prevention, and recurrence inhibition compared to current treatments.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Malignant tumors pose a significant global health challenge, driving the need for novel cancer treatments.
- Oncolytic therapy offers a promising approach, but faces challenges like safety, targeted delivery, and immunosuppression.
- Existing oncolytic agents, including bacteria, viruses, and peptides, have limitations in clinical translation.
Purpose of the Study:
- To develop advanced oncolytic agents overcoming current therapeutic limitations.
- To engineer biomimetic nano-systems inspired by oncolytic bacteria (OBNs).
- To evaluate the efficacy and mechanisms of OBNs in preclinical cancer models.
Main Methods:
- Designed OBNs using biomimetic nanoengineering, incorporating bacterial cell wall mimics, acidity-switchable elements, and tryptophan-rich peptides.
- Encapsulated immunomodulators within OBNs to enhance immunotherapy.
- Investigated OBNs' multimodal imaging capabilities for biological tracing.
- Assessed OBNs' performance via systemic administration in preclinical models, comparing them to intratumoral injections of oncolytic peptides.
Main Results:
- OBNs demonstrated inherent oncolytic potential with enhanced tumor targeting and circulation.
- Systemic administration of d-chiral OBNs exhibited superior oncolytic efficacy over clinical-grade oncolytic peptides.
- OBNs effectively suppressed primary tumors, prevented metastasis, and inhibited recurrence.
- OBNs possess multimodal imaging potential for tracking and biological tracing.
Conclusions:
- Biomimetic nanoengineering offers a powerful strategy for developing next-generation oncolytic agents.
- OBNs represent a significant advancement in oncolytic therapy, addressing key challenges in safety, efficacy, and delivery.
- This innovative approach holds promise for revolutionizing cancer treatment paradigms and clinical translation.
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