Bacteria-Driven Hypoxia Targeting for Combined Biotherapy and Photothermal Therapy

Abstract

The facultative anaerobe Salmonella strain VNP20009 selectively colonizes into tumors following systemic injection due to its preference for the hypoxia in the tumor cores. However, the phase 1 clinical trial of VNP20009 has been terminated mainly due to its weak antitumor effects and exhibition of dose-dependent toxicity. Here, we leveraged the advantages of VNP20009 biotherapy together with polydopamine-mediated photothermal therapy in order to enhance the antitumor efficacy toward malignant melanoma. VNP20009 was coated with polydopamine via oxidation and self-polymerization, which was then injected into tumor-bearing mice via the tail vein. Polydopamine-coated VNP20009 targeted hypoxic areas of the solid tumors, and near-infrared laser irradiation of the tumors induced heating due to polydopamine. This combined approach eliminated the tumors without relapse or metastasis with only one injection and laser irradiation. More importantly, we found both VNP and pDA potentiate the therapeutic ability of each other, resulting in a superior anticancer effect.

Chemotaxis-driven delivery of nano-pathogenoids for complete eradication of tumors post-phototherapy

“…8i), possibly due to the acute enteritis induced by PAMPs on OMVs (such as LPS) 54 . Such OMVs toxicity issues can be addressed by using bacteria strains with lower pathogenicity or genetically modified attenuated bacteria strains with, for example, impaired LPS signaling 40,55 .…”

Self‐Mineralized Photothermal Bacteria Hybridizing with Mitochondria‐Targeted Metal–Organic Frameworks for Augmenting Photothermal Tumor Therapy

“…According to the dilution coating method on Luria–Bertani (LB) agar plates (Figure 3E), the comparative bacterial colony‐forming units of PTB@ZIF‐90/MB and PTB in dark condition indicated that decoration of ZIF‐90/MB on PTB surface negligibly affected bacterial activity. However, the bacterial colony‐forming units sharply decreased when PTB@ZIF‐90/MB suffered from either 660 nm light illumination or 808 nm laser irradiation or both, revealing that 1 O 2 and high temperature certainly suppressed bacterial activity, which could support in vivo biosafety 10,34. The mobility of PTB@ZIF‐90/MB was studied by a semi‐solid medium puncture assay (Figure S13, Supporting Information) 35.…”

“…Additionally, bacteria are convenient to be chemically modified because of abundant chemical groups presenting on their surface 1,8. Given these advantages, versatile bacteria‐based tumor therapeutic platforms are promising to tackle significant challenges in tumor therapy 5,9–12…”

Mitochondria‐Targeted Polydopamine Nanocomposite with AIE Photosensitizer for Image‐Guided Photodynamic and Photothermal Tumor Ablation

“…Benefit from the enrichment of catechol and phenyl structure, PDA has a sticky surface and can stick many substances through hydrogen bond and π–π interaction . Besides, PDA can be used in photothermal therapy (PTT) on the base of photothermal conversion ability . The reported mitochondria‐targeting AIE PSs for PDT treatment only show good ablation effect for cancerous cells, not for tumors .…”