Tumor agnostic ultrasmall nanoprobes for fluorescence-guided surgical resection in peritoneal metastasis.

PURPOSE

Surgical excision of metastases is the only curative treatment strategy in peritoneal carcinomatosis management, and the completeness of tumor resection determines the success of the surgery. Tumor-specific fluorescence-guided probes can improve the outcomes of cytoreductive surgery and thereby prognosis. This study aimed to develop and evaluate the feasibility of fluorescently labeled ultrasmall porous silica nanoparticles (UPSN) for image-guided resection of peritoneally disseminated tumors of different origins.

METHODS

Ultrasmall fluorescent nanoprobes were synthesized and characterized for their physicochemical properties and stability. Tumor-specific uptake and biodistribution profiles were evaluated in syngeneic CT26 colorectal and KPC-689 pancreatic cancer murine models. The practicability of real-time optical UPSN-guided resection was examined in the CT26 colorectal cancer model using a surgical stereomicroscope. Quantitative measurements of tumor sensitivity and specificity were performed. Histopathological examination validated in vivo findings about tumor-specific accumulation and safety of ultrasmall fluorescent probes.

RESULTS

As-synthesized UPSNs were successfully surface modified with Cy5 or Cy3 dyes maintaining sub-15 nm size and near neutral charge which is beneficial for optimized in vivo pharmacokinetics. UPSN-Cy5 demonstrated high tumor-specific uptake and favorable biodistribution profiles in peritoneal metastasis models of CT26 and KPC tumors. Dye-conjugated UPSN enabled resection of microscopic lesions and achieved a higher tumor-to-background ratios in comparison to FDA-approved indocyanine green (ICG) dye in both models. Microscopic evaluation showed tumor localization and off-target safety profile of the UPSN-Cy5.

CONCLUSION

Ultrasmall fluorescent probes were effective in surgical resection of peritoneal metastases with high sensitivity and specificity, thus emerging as promising tumor agnostic agents for image-guided cancer surgery.