Critical clinical gaps in cancer precision nanomedicine development

Recent Progress and Trends in X-ray-Induced Photodynamic Therapy with Low Radiation Doses

“…It could be inferred that the nanomaterials composed of heavy metals of Gd and Hf should be suitable candidates to move to clinical trials, while the rest should be further evaluated until the biocompatibility and safety are fully estimated. The leading reasons for Hf- or Gd-based nanomaterials for use as radiosensitizers are their strong interaction with X-rays and low cytotoxicity. ,− Other characteristics that the nanomaterials or candidates should maintain for clinical use include rational nanomaterial design (e.g., size smaller than 6 nm for rapid clearance by renal, spherical, or rod shape within 20–150 nm to allow metabolism through liver, neutral and negatively charged surface or biocompatible polymer modification) to guarantee long-term biodistribution, passive or active tumor targeting, sufficient tumor accumulation, microenvironment response, and efficient clearance with minimized toxicity risks. − Notably, the applications of Cu-Cy nanoformulations for X-PDT, gold clustoluminogens for X-PDT (1 Gy), as well as the AGuIX for clinical trials indicate that metal complexes-based nanoformulations contain huge potential. Under such circumstances, we infer that Zr- or Bi-based nanoformulations might be suitable translatable candidates for X-PDT because they both have strong interactions with X-rays and can form diverse types of complexes or ultrasmall nanostructures. , Of note, the preclinical or clinical toxicity should be always evaluated beyond the general hemolysis test, hematoxylin and eosin (H&E) staining or metabolomics, , or the procedures such as genotoxicity testing, carcinogenicity testing, neurotoxicity testing, etc .…”

“…As the practical active targeting efficiency and the enhanced permeability and retention effect have been challenged in recent years, the delivery and accumulation of nanoformulations in deep-seated tissues should also not be neglected. Notably, despite active targeting has been proved in basic research to be quite effective, ,,, and an active tumor-targeted nanomedicine, Ontak, has been approved by FDA in treading cutaneous T-cell lymphoma, the general trend of nanoformulations under clinical trials is using passive accumulation via the EPR effect, as in most cases that active tumor targeting failed their clinical trials due to less efficient tumor targeting outcomes (e.g., MM-302 and Bind-014) . Therefore, the future trend of nanomedicine should consider the advantages of both active and passive targeting in nanoformulation design with optimal components.…”

Poly lactic‐co‐glycolic acid‐alginate nanocarrier for efficient drug delivery to liver cancer cells

“…These factors are including race, gender, chronic viral hepatitis (hepatitis B and C virus), fatty liver disease, inherited metabolic diseases, alcohol-related cirrhosis, smoking, obesity, type 2 diabetes, and exposure to a chronic toxin (like aflatoxin) [5,6]. There are a number of conventional modalities, such as surgery, chemotherapy, hormone therapy, radiotherapy, and thermal therapy, to inhibit the progression of liver cancer; however, deficiencies and restrictions of these methods have resulted in their less effectiveness [7][8][9]. For example, very low specificity, high repetition during the treatment stages, multi-drug resistance, high side effects, weak stability in the human body serum, and less costeffectiveness are mentioned as unavoidable drawbacks of the above-mentioned modalities in the treatment of cancer [10,11].…”

Site-specific Activation of Mitochondria-Targeting Peptide Nanomaterials for Treatment of Drug-Resistant Tumors

“…In addition to the enhancement of drug sensitivity, the increase of intracellular levels of the active drug is also essential for effective therapy in drug-resistant tumors. Given the differences between tumor cells and normal cells, many targeted drug delivery systems have been explored, wherein the targeting ligands are incorporated. − However, whether designing a single targeted system or multiple targeted systems, it only integrates the targeting ligands onto the carrier and suffers from non-selectivity and off-target problems. , In addition to the variable design of targeting ligands, the selective drug activation strategies responding to the tumor microenvironment are often reported, such as reactive oxygen species (ROS), glutathione (GSH), and pH responsive drug activation. The high intracellular GSH concentration and lysosome acidic pH in normal and cancer cells make the ROS-responsive drug activation strategy more conducive to selective targeting of tumor cells .…”