Evolution from small molecule to nano-drug delivery systems:An emerging approach for cancer therapy of ursolic acid

Ursolic acid(UA),a natural pentacyclic triterpenoid,possesses widespread biological and pharmacological activities.However,drawbacks such as low bioavailability,poor targeting and rapid metabolism greatly hinder its further clinical application.Recently,with the development of nanotechnology,various UA nanosystems have emerged as promising strategies for effective cancer therapy.This article reviews various types of UA-based nanodelivery systems,primarily with emphasis placed on novel UA-based carrier-free nanodrugs,which are considered to be innovative methods for cancer therapy.Moreover,this review presents carrier-free nano-drugs that co-assembled of UA and photosensitizers that displayed synergistic antitumor performance.Finally,the article also describes the development and challenges of UA nanosystems for future research in this field.Overall,the information presented in this review will provide new insight into the rational utilization of nano-drugs in cancer therapy.

Cancer metastasis chemoprevention prevents circulating tumour cells from germination

The war against cancer traces back to the signature event half-a-century ago when the US National Cancer Act was signed into law.The cancer crusade costs trillions with disappointing returns,teasing the possibility of a new breakthrough.Cure for cancer post-metastases still seems tantalisingly out of reach.Once metastasized,cancer-related death is extremely difficult,if not impossible,to be reversed.Here we present cancer pre-metastasis chemoprevention strategy that can prevent circulating tumour cells(CTCs)from initiating metastases safely and effectively,and is disparate from the traditional cancer chemotherapy and cancer chemoprevention.Deep learning of the biology of CTCs and their disseminating organotropism,complexity of their adhesion to endothelial niche reveals that if the adhesion of CTCs to their metastasis niche(the first and the most important part in cancer metastatic cascade)can be pharmaceutically interrupted,the lethal metastatic cascade could be prevented from getting initiated.We analyse the key inflammatory and adhesive factors contributing to CTC adhesion/germination,provide pharmacological fundamentals for abortifacients to intervene CTC adhesion to the distant metastasis sites.The adhesion/inhibition ratio(AIR)is defined for selecting the best cancer metastasis chemopreventive candidates.The successful development of such new therapeutic modalities for cancer metastasis chemoprevention has great potential to revolutionise the current ineffective post-metastasis treatments.

Downregulation of KCTD12 contributes to melanoma stemness by modulating CD271

Objective: Cancer metastasis remains the primary cause of cancer-related death worldwide.In a previous study, we found that levels of BTB/POZ domain-containing protein KCTD12 are lower in metastatic melanoma cells than in parental melanoma cells.The purpose of this study was to identify the roles of KCTD12 in cancer metastasis.Methods: The Cancer Genome Atlas(TCGA) datasets were used to evaluate the relationship between KCTD12 and skin cutaneous melanoma(SKCM) prognosis.The effects of endogenous KCTD12 on biological behaviors were examined using the MTT assay.The impacts of KCTD12 on melanoma stemness were explored using spheroid formation assay.KCTD12 knockout A375 cells were generated to confirm the inhibitory effect of KCTD12 on CD271, and a mouse metastatic model was used to determine the impact of KCTD12 on melanoma metastasis in vivo.Results: KCTD12 levels were lower in lung metastatic cells than in paired parental melanoma cells, and low KCTD12 expression indicated a poor prognosis in SKCM.Cancer metastasis-related capacities were higher in lung metastatic cells than in parental melanoma cells.Moreover, KCTD12 knockdown enhanced tumor growth and metastasis both in vitro and in vivo.Mechanistically, the interaction between KCTD12 and CD271 might be responsible for the stemness transformation after KCTD12 knockdown.Conclusions: This study identifies for the first time the role of the interaction between KCTD12 and CD271 in inducing melanoma cell stemness transformation.Moreover, KCTD12 repression enhances melanoma cell growth, adhesion, migration and invasion.

Achyranthes bidentata polysaccharide can safely prevent NSCLC metastasis via targeting EGFR and EMT

Dear Editor,Cancer metastasis,dissemination of cancer cells from primary tumors to distant sites,attributes to 90%cancer-related death.1 Although the targeted therapies,bio-nanomaterial-based target delivery,and the consequent adoption of the so-called personalized medicine have obtained notable achievements in some cancers,significant problems still exist with these approaches.2 There are hardly any cancer therapeutic agents that can interfere with metastasized cancer.In recent times,we proposed a novel concept,namely cancer metastasis chemoprevention,which is different from the existing cancer chemotherapy and cancer chemoprevention.Cancer metastasis chemoprevention aims at safely preventing circulating tumor cells(CTCs)and related molecules from gemmating into the metastatic tissues.The strategy does not intend to kill cancer cells as cancer chemotherapy does,nor to aimlessly prevent cancers from carcinogenesis as cancer chemoprevention does.

NOL7 facilitates melanoma progression and metastasis

Dear Editor,Metastasis is the cause of most fatalities in cancer patients and remains the phenomenon poorly understood mechanistically. Deciphering of the regulatory networks underlying the cancer cell metastasis is urgently needed. Nucleolar protein 7 (NOL7) has been reported to function as a tumor suppressor in cervical cancer.1 Our current study reveals a novel tumor-promoting capacity of NOL7 in melanoma. We first detected that NOL7 expression is upregulated in metastatic melanoma as compared with its expression at the primary site through isobaric tag for relative and absolute quantitation proteomic screening, further confirming this finding with the analysis of NOL7 protein and messenger RNA (mRNA) levels (Supplementary Fig. S1). Importantly, NOL7 expression increased with the disease progression from benign nevus to primary melanoma and further to metastatic melanoma (Fig. 1a and Supplementary Fig. S1d). Previous studies have shown that melanoma is commonly associated with the amplification of the chromosome region 6p, particularly 6p21–23, where the NOL7 gene resides, and that this region frequently undergoes heterozygous loss in cervical cancer.2 It might therefore be predicted that NOL7 exhibits a different expression pattern and plays different roles in melanoma and cervical cancer.

Combination of Se-methylselenocysteine,D-α-tocopheryl succinate,β-carotene,and L-lysine can prevent cancer metastases using as an adjuvant therapy

Objective:Primary tumor treatment through surgical resection and adjuvant therapy has been extensively studied,but there is a lack of effective strategies and drugs for the treatment of tumor metastases.Here,we describe a functional product based on a combination of compounds,which can be used as an adjuvant therapy and has well-known mechanisms for inhibiting cancer metastases,improving anti-cancer treatment,and enhancing immunity and antioxidant capacity.Our designed combination,named MVBL,consists of four inexpensive compounds:L-selenium-methylselenocysteine(MSC),D-α-tocopheryl succinic acid(VES),β-carotene(β-Ca),and L-lysine(Lys).Methods:The effects of MVBL on cell viability,cell cycle,cell apoptosis,cell migration,cell invasion,reactive oxygen species(ROS),and paclitaxel(PTX)-combined treatment were studied in vitro.The inhibition of tumor metastasis,antioxidation,and immune enhancement capacity of MVBL were determined in vivo.Results:MVBL exhibited higher toxicity to tumor cells than to normal cells.It did not significantly affect the cell cycle of cancer cells,but increased their apoptosis.Wound healing,adhesion,and transwell assays showed that MVBL significantly inhibited tumor cell migration,adhesion,and invasion.MVBL sensitized MDA-MB-231 breast cancer cells to PTX,indicating that it can be used as an adjuvant to enhance the therapeutic effect of chemotherapy drugs.In mice,experimental data showed that MVBL inhibited tumor metastasis,prolonged their survival time,and enhanced their antioxidant capacity and immune function.Conclusions:This study revealed the roles of MVBL in improving immunity and antioxidation,preventing tumor growth,and inhibiting metastasis in vitro and in vivo.MVBL may be used as an adjuvant drug in cancer therapy for improving the survival and quality of life of cancer patients.

Recent progress in sono-photodynamic cancer therapy:From developed new sensitizers to nanotechnology-based efficacy-enhancing strategies

Many sensitizers have not only photodynamic effects,but also sonodynamic effects.Therefore,the combination of sonodynamic therapy(SDT)and photodynamic therapy(PDT)using sensitizers for sonophotodynamic therapy(SPDT)provides alternative opportunities for clinical cancer therapy.Although significant advances have been made in synthesizing new sensitizers for SPDT,few of them are successfully applied in clinical settings.The anti-tumor effects of the sensitizers are restricted by the lack of tumor-targeting specificity,incapability in deep intratumoral delivery,and the deteriorating tumor microenvironment.The application of nanotechnology-based drug delivery systems(NDDSs)can solve the above shortcomings,thereby improving the SPDT efficacy.This review summarizes various sensitizers as sono/photosensitizers that can be further used in SPDT,and describes different strategies for enhancing tumor treatment by NDDSs,such as overcoming biological barriers,improving tumor-targeted delivery and intratumoral delivery,providing stimuli-responsive controlled-release characteristics,stimulating anti-tumor immunity,increasing oxygen supply,employing different therapeutic modalities,and combining diagnosis and treatment.The challenges and prospects for further development of intelligent sensitizers and translational NDDSs for SPDT are also discussed.

Nucleic acids analysis

Nucleic acids are natural biopolymers of nucleotides that store, encode, transmit and express genetic information, which play central roles in diverse cellular events and diseases in living things. The analysis of nucleic acids and nucleic acids-based analysis have been widely applied in biological studies, clinical diagnosis, environmental analysis, food safety and forensic analysis.During the past decades, the field of nucleic acids analysis has been rapidly advancing with many technological breakthroughs.In this review, we focus on the methods developed for analyzing nucleic acids, nucleic acids-based analysis, device for nucleic acids analysis, and applications of nucleic acids analysis. The representative strategies for the development of new nucleic acids analysis in this field are summarized, and key advantages and possible limitations are discussed. Finally, a brief perspective on existing challenges and further research development is provided.