Recent advances in cancer therapeutics, such as targeted therapy and immunotherapy, have raised the hope for cures for many cancer types. However, there are still ongoing challenges to the pursuit of novel therapeutic approaches, including high toxicity to normal tissue and cells, difficulties in treating deep tumor tissue, and the possibility of drug resistance in tumor cells. The use of live tumor-targeting bacteria provides a unique therapeutic option that meets these challenges. Compared with most other therapeutics, tumor-targeting bacteria have versatile capabilities for suppressing cancer. Bacteria preferentially accumulate and proliferate within tumors, where they can initiate antitumor immune responses. Bacteria can be further programmed via simple genetic manipulation or sophisticated synthetic bioengineering to produce and deliver anticancer agents based on clinical needs. Therapeutic approaches using live tumor-targeting bacteria can be applied either as a monotherapy or in combination with other anticancer therapies to achieve better clinical outcomes. In this review, we introduce and summarize the potential benefits and challenges of this anticancer approach. We further discuss how live bacteria interact with tumor microenvironments to induce tumor regression. We also provide examples of different methods for engineering bacteria to improve efficacy and safety. Finally, we introduce past and ongoing clinical trials involving tumor-targeting bacteria.

The aberrant proliferation of tumor cells and abundant vasculature in tumor tissues are closely correlated with receptors that are specifically dysregulated in tumor cells. These tumor-associated targets are critical in early diagnosis and therapy selection. Ligands such as antibodies, proteins, polypeptides and polysaccharides that specifically bind to these targets can significantly improve the detection and cure rate when used as tumor imaging probes or anti-tumor agents. Compared to other targeting ligands, peptides have attracted increasingly more attention in tumor diagnostics and therapeutics because of their small sizes, high affinity, stability, ease of modification and low immunogenicity. Several peptide-based imaging probes and therapeutic agents have already been used in clinical trials. This review summarizes some of the tumor-associated targets and their corresponding peptides, as well as the potential of these peptides in cancer treatment.

Photoacoustic imaging (PAI) is a new and attractive imaging modality, and it has strong potential for application in the early detection of tumors through the use of optically absorbing targeted contrast agents. Ag2S quantum dots (QD) are a promising bionanomaterial and have attracted significant attention in the field of bioimaging. In this study, water-soluble and carboxylic acid group-coated Ag2S QDs with an ultrasmall size (∼8 nm) were synthesized via a one-step method. Their surface plasmon resonance wavelength was determined to be ∼800 nm, which is ideal for PAI. Ag2S QDs were then modified with the epidermal growth factor receptor 1 (EGFR) targeted small protein affibody ZEGFR:1907. The resulted nanoprobe, ZEGFR:1907-Ag2S QDs, was then used for targeted PAI of EGFR-overexpressed tumors. The biodistribution of the nanoprobe was further measured by ex vivo near infrared fluorescence (NIRF) imaging of the dissected tissues. The PAI results showed that ZEGFR:1907-Ag2S QDs specifically image EGFR positive tumors. The biodistribution study revealed that the nanoprobe mainly accumulated in the liver, spleen and tumors; tissue H&E staining studies indicated that the probe has good biocompatibility. Overall, the affibody-functionalized Ag2S QDs are a novel targeted nanoprobe that can be used for specific PAI of tumors.