Exploiting acidic tumor microenvironment for the development of novel cancer nano-theranostics

(Nanowerk News) Cancer is one of leading causes of human mortality around the world. The current mainstream cancer treatment modalities (e.g. surgery, chemotherapy and radiotherapy) only show limited treatment outcomes, partly owing to the complexities and heterogeneity of tumor biology. In the recent several decades, with the rapid advance of nanotechnology, nanomedicine has attracted more and more attentions and been exploited as a promising candidate for personalized medicine to enable more efficient and reliable cancer diagnosis and treatment.
Unlike normal cells energized via the oxidative phosphorylation, tumor cells utilize the energy produced from the oxygen independent glycolysis for survival by adapting to insufficient tumor oxygen supply resulted from the heterogeneously distributed tumor vasculatures (also known as the Warburg effect). Via such oncogenic metabolism, tumor cells would produce a large amount of lactate along with excess protons and carbon dioxide, which collectively contribute to enhanced acidification of the extracellular TME with pH often in the range of 6.5-6.8, leading to increased tumor metastasis and treatment resistance.
To date, with the fast advance of nanotechnology, several different catalogs of nanomaterials including both organic polymers and inorganic nanomaterials with excellent tumor acidic pH responsive transition in their physicochemical properties (e.g. surface charge, sizes, etc.), acid-triggered cleavage of covalent bonds, as well as acid-triggered decomposition behaviors, have been widely explored for design of various different types of cancer-targeted nano-theranostics.
Size switchable nano-theranostics constructed with decomposable inorganic nanomaterials for acidic TME targeted cancer therapy. (a) A scheme showing the preparation of HSA-MnO2-Ce6&Pt (HMCP) nanoparticles, and (b) their tumor microenvironment responsive dissociation to enable efficient intra-tumoral penetration of therapeutic albumin complexes. (c) A scheme showing the preparation of Ce6(Mn)@CaCO3-PEG, and (d) its acidic TME responsive dissociation for enhanced MR imaging and synergistic cancer therapy. (© Science China Press) (click on image to enlarge)
In a new overview published in the Beijing-based National Science Review ("The acidic tumor microenvironment: a target for smart cancer nano-theranostics"), co-authors Liangzhu Feng, Ziliang Dong, Danlei Tao, Yicheng Zhang and Zhuang Liu at the Institute of Functional Nano & Soft Materials (FUNSOM), Soochow University in Suzhou, China present the up-to-date progresses in the design of novel multifunctional nano-theranostics for precision cancer nanomedicine by targeting the unique acidic TME.
These scientists likewise outline the potential development directions of future acidic tumor microenvironments responsive nano-theranostics.
"Various types of pH-responsive nanoprobes have been developed to enable great signal amplification under slightly reduced pH within solid tumors. By taking the acidic TME as the target, smart imaging nanoprobes with excellent pH responsive signal amplification would be promising to enable more sensitive and accurate tumor diagnosis," they state in their article.
"As far as nano-therapeutics are concerned, it has been found that the acidic TME responsive surface charge reverse, PEG corona detachment and size shrinkage (or decomposition) of nanoparticles would facilitate the efficient tumor accumulation, intra-tumoral diffusion and tumor cellular uptake of therapeutics, leading to significantly improved cancer treatment. Therefore, the rational development of novel cancer targeted nano-theranostics with sequential patterns of size switch from large to small, and surface charge reverse from neutral or slightly negative to positive within the tumor, would be more preferred for efficient tumor-targeted drug delivery."
Apart from the illustration of those state-of-the-art fundamental researches, the scientists also indicated that "for the translation of those interesting smart pH-responsive nano-therapeutics from bench to bedside, the formulation of those nanoscale systems should be relatively simple, reliable and with great biocompatibility since many of those currently developed nano-theranostics were may be too complicated for clinical translation."
Source: Science China Press