Systemic metastasis-targeted nanotherapeutic reinforces tumor surgical resection and chemotherapy

Abstract

Failure of conventional clinical therapies such as tumor resection and chemotherapy are mainly due to the ineffective control of tumor metastasis. Metastasis consists of three steps: (i) tumor cells extravasate from the primary sites into the circulation system via epithelial-mesenchymal transition (EMT), (ii) the circulating tumor cells (CTCs) form “micro-thrombi” with platelets to evade the immune surveillance in circulation, and (iii) the CTCs colonize in the pre-metastatic niche. Here, we design a systemic metastasis-targeted nanotherapeutic (H@CaPP) composed of an anti-inflammatory agent, piceatannol, and an anti-thrombotic agent, low molecular weight heparin, to hinder the multiple steps of tumor metastasis. H@CaPP is found efficiently impeded EMT, inhibited the formation of “micro-thrombi”, and prevented the development of pre-metastatic niche. When combined with surgical resection or chemotherapy, H@CaPP efficiently inhibits tumor metastasis and prolonged overall survival of tumor-bearing mice. Collectively, we provide a simple and effective systemic metastasis-targeted nanotherapeutic for combating tumor metastasis.

Nanotechnology-aided advancement in the combating of cancer metastasis

“…They used a targeted lipid NP to deliver miR-671-5p to target the noncoding CDR1as/CDR1 axis and inhibited lymphatic metastatic spread in vivo in mice. Xu et al [ 29 ] developed a systemic metastasis-targeted nanotherapeutic (H@CaPP) for co-delivering an anti-inflammatory agent, piceatannol, and an anti-thrombotic agent, low molecular weight heparin, to the primary tumor site to impede the multiple steps of tumor metastasis. This nanoformulation efficiently hindered EMT, inhibited the formation of “micro-thrombi”, and prevented the development of pre-metastatic niche.…”

“…Targeting early metastasis opens promising therapeutic avenues for metastasis prevention. As mentioned above, nanotherapeutic H@CaPP co-delivering piceatannol and heparin impedes EMT, the formation of “micro-thrombi”, and the development of pre-metastatic niche, thus inhibiting lung metastasis in breast tumor-bearing mice [ 29 ]. This could be a promising strategy; however, the use of anticoagulants as a specific metastasis prevention strategy should be considered with caution in human translation studies given the risk of bleeding complications.…”

A Living Material Constructed from Stem Cells for Tumor‐Tropic Oncotherapy with Real‐Time Imaging

“…[ 1 ] Currently, the most acceptable treatments for cancers are surgical resection and chemotherapy. [ 2 ] Normally, surgical resection cannot eradicate dispersed tumor microsatellites; therefore, chemotherapy is necessary. However, conventional chemotherapy lacks selectivity, causing similar damage to healthy tissues.…”

“…[1] Currently, the most acceptable treatments for cancers are surgical resection and chemotherapy. [2] Normally, surgical resection cannot eradicate dispersed tumor microsatellites; therefore, chemotherapy is necessary. However, conventional chemotherapy lacks in response to tumor-secreted chemoattractants, angiogenic factors, and/or inflammatory signals, making them attractive candidates for targeted drug delivery vehicles.…”

Engineering a multi-target therapy nanoplatform against tumor growth and metastasis via a novel NSAID-Pt(iv) prodrug

“…For example, surgery will cause the release of immunosuppressive factors and VEGF to promote cancer metastasis. 6 Therefore, finding effective methods to fight tumor metastasis from multiple points is an urgent problem.…”