Smart Nanogatekeepers for Tumor Theranostics

Abstract

early tumor mass efficiently, but a single surgical approach seems incompetent for advanced tumor tissues with serious distant metastasis. Surgery cannot completely remove all primary and metastatic tumor cells, thereby generating a high recurrence risk. [2] High-energy radioactive rays are utilized to destroy DNA and protein structures and inhibit there functions in these exposed tumor cells. However, it should be noted that this local irradiationtriggered therapy modality does not distinguish cancer from other tissues, which could induce fatal destruction in circumambient normal tissues. Immunotherapy is an emerging modality that relies on the human immune system and provides a robust defense against advanced and metastatic tumors. [3] Immune checkpoint blockade (ICB) therapy, for example, promotes a systemic immune response that suppresses tumor growth and recurrence by blocking the overexpressed programmed cell death ligand 1 (PD-L1) [4] and CD47 [5] in tumor cells, or cytotoxic T lymphocyte (CTL) associated antigen 4 (CTLA-4) in T cells. [6] Several ICB antibodies, such as pembrolizumab and nivolumab, have been approved by the Food and Drug Administration of the USA (FDA) to treat metastatic colorectal cancer (CRC). [7] Unfortunately, clinical trials revealed that only a fraction of patients with clinical cancer respond to this emerging immunotherapy [8] although this poor efficiency is mainly ascribed to insufficient T cell infiltration [9] and undesirable immunosuppressive microenvironments. [10] Compared to surgery, radiotherapy, and immunotherapy, chemotherapy is preferable as monotherapy or synergetic therapy with the above modalities for cancer treatment. In general, current chemotherapeutic formulations are categorized as solutions and nanoformulations. For example, chemotherapeutic solutions such as Taxel and Doxil are used clinically, but the undesirable selectivity and serious toxicity significantly hinder further application. Compared to solutions, nanoformulations exhibit increased drug accumulation in tumor tissue due to the enhanced permeability and retention (EPR) effect. Specifically, paclitaxel (PTX)-derived Nanoxel shows a higher tumor regression profile than Taxol solution, with improved safety. [11] In addition to EPR-mediated passive accumulation, a liganddirected targeting strategy is also employed in developing nanoparticle (NP) delivery systems as this enables specific ligand-receptor interactions for NP accumulation. [12] To date, numerous tumor microenvironment-sensitive deshielding nanosystems have been fabricated to realize stealth-targeting Nanoparticulate drug delivery systems (nano-DDSs) are required to reliably arrive and persistently reside at the tumor site with minimal off-target side effects for clinical theranostics. However, due to the complicated environment and high interstitial pressure in tumor tissue, they can return to the bloodstream and cause secondary side effects in normal organs. Recently, a number of nanogatekeepers have been engineered via structure-transf...

Implications of hydrogen sulfide in colorectal cancer: Mechanistic insights and diagnostic and therapeutic strategies

“…The development of tumor-targeted intelligent diagnostic and therapeutic drugs based on TME characteristics is currently a popular cancer treatment strategy [ 218 , [303] , [304] , [305] , [306] ]. The high level of H 2 S in CRC cells makes it a promising endogenous microenvironment molecule for the design and synthesis of H 2 S-responsive diagnostic therapeutics targeting CRC.…”