Improving cancer therapy by combining cell biological, physical, and molecular targeting strategies

Successful cancer therapy depends on selective killing of tumor cells while sparing normal cells. Selectivity can be achieved through treatment strategies that target tumor cells. A recent report from the Li laboratory （1） describes an elegant strategy to selectively kill tumor cells by combining several targeting strategies based on cell biological, physical, and molecular （genetic） properties of tumor and normal cells that enhances tumor cell killing in vitro and in an in vivo tumor xenograft model. The idea of using a multiplex targeting approach is reminiscent of strategies in which several antibiotics are used to treat bacterial infections while minimizing the chance that rare antibiotic-resistant mutants will arise within a population.

Hollow mesoporous polyaniline nanoparticles with high drug payload and robust photothermal capability for cancer combination therapy

In recent years,synergistic chemo-photothermal therapy has revealed promising potential in treatments against various kinds of cancer.However,the development of superb photothermal agents with high drug loading capacity is still highly required.In this work,a hollow mesoporous polyaniline nanoparticle(HPANI NP)has been developed for encapsulating chemotherapeutic drug doxorubicin(DOX)with an remarkable drug loading content as high as 37.5%.Additional PEG modification endowed the drugloaded HPANI NPs with improved water-dispersibility and bioavailability.Such PEG-HPANI-DOX NPs exhibited strong NIR absorbance and robust photothermal conversion capacity,exhibiting highly efficient synergistic cancer treatment.More interestingly,the responsively released DOX molecules could emit strong red fluorescence,which could be employed to monitor the cellular endocytosis and drug release profile of PEG-HPANI-DOX NPs.Finally,the as-fabricated NPs showed good biocompatibility and low toxicity,serving as a promising nanoagent for highly efficient drug delivery and cancer combination therapy.

Enhancing metformin-induced tumor metabolism destruction by glucose oxidase for triple-combination therapy

Despite decades of laboratory and clinical trials,breast cancer remains the main cause of cancer-related disease burden in women.Considering the metabolism destruction effect of metformin(Met)and cancer cell starvation induced by glucose oxidase(GOx),after their efficient delivery to tumor sites,GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in situ.Herein,a pH-responsive epigallocatechin gallate(EGCG)-conjugated low-molecular-weight chitosan(LC-EGCG,LE)nanoparticle(Met–GOx/Fe@LE NPs)was constructed.The coordination between iron ions(Fe3+)and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton reaction.Met–GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its stability.Moreover,this pH-responsive nanoplatform presents controllable drug release behavior.An in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nanoplatform was 3.6-fold higher than that of the free drug.The in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their proliferation.This triple-combination therapy approach is promising for efficient and targeted cancer treatment.

Advances in drug delivery system for platinum agents based combination therapy

Platinum-based anticancer agents are widely used as first-line drugs in cancer chemotherapy for various solid tumors. However, great side effects and occurrence of resistance remain as the major drawbacks for almost all the platinum drugs developed. To conquer these problems, new strategies should be adopted for platinum drug based chemotherapy. Modern nanotechnology has been widely employed in the delivery of various therapeutics and diagnostic. It provides the possibility of targeted delivery of a certain anticancer drug to the tumor site, which could minimize toxicity and optimize the drug efficacy. Here, in this review, we focused on the recent progress in polymer based drug delivery systems for platinum-based combination therapy.

Micelles as potential drug delivery systems for colorectal cancer treatment

Despite the significant progress in cancer therapy,colorectal cancer(CRC)remains one of the most fatal malignancies worldwide.Chemotherapy is currently the mainstay therapeutic modality adopted for CRC treatment.However,the long-term effectiveness of chemotherapeutic drugs has been hampered by their low bioavailability,non-selective tumor targeting mechanisms,non-specific biodistribution associated with low drug concentrations at the tumor site and undesirable side effects.Over the last decade,there has been increasing interest in using nanotechnology-based drug delivery systems to circumvent these limitations.Various nanoparticles have been developed for delivering chemotherapeutic drugs among which polymeric micelles are attractive candidates.Polymeric micelles are biocompatible nanocarriers that can bypass the biological barriers and preferentially accumulate in tumors via the enhanced permeability and retention effect.They can be easily engineered with stimuli-responsive and tumor targeting moieties to further ensure their selective uptake by cancer cells and controlled drug release at the desirable tumor site.They have been shown to effectively improve the pharmacokinetic properties of chemotherapeutic drugs and enhance their safety profile and anticancer efficacy in different types of cancer.Given that combination therapy is the new strategy implemented in cancer therapy,polymeric micelles are suitable for multidrug delivery and allow drugs to act concurrently at the action site to achieve synergistic therapeutic outcomes.They also allow the delivery of anticancer genetic material along with chemotherapy drugs offering a novel approach for CRC therapy.Here,we highlight the properties of polymeric micelles that make them promising drug delivery systems for CRC treatment.We also review their application in CRC chemotherapy and gene therapy as well as in combination cancer chemotherapy.

Cancer immunity and therapy using hyperthermia with immunotherapy, radiotherapy, chemotherapy, and surgery

Hyperthermia is a type of medical modality for cancer treatment using the biological effect of artificially induced heat.Even though the intrinsic effects of elevated body temperature in cancer tissues are poorly understood,increasing the temperature of the body has been recognized as a popular therapeutic method for tumorous lesions as well as infectious diseases since ancient times.Recently accumulated evidence has shown that hyperthermia amplifies immune responses in the body against cancer while decreasing the immune suppression and immune escape of cancer.It also shows that hyperthermia inhibits the repair of damaged cancer cells after chemotherapy or radiotherapy.These perceptions indicate that hyperthermia has potential for cancer therapy in conjunction with immunotherapy,chemotherapy,radiotherapy,and surgery.Paradoxically,the anticancer effect of hyperthermia alone has not yet been adequately exploited because deep heating techniques and devices to aggregate heat effects only in cancer tissues are difficult in practical terms.This review article focuses on the current understanding concerning cancer immunity and involvement of hyperthermia and the innate and adoptive immune system.The potential for combination therapy with hyperthermia and chemotherapy,radiotherapy,and surgery is also discussed.

Bioresponsive cisplatin crosslinked albumin hydrogel served for efficient cancer combination therapy

Combination therapy is one of the potential strategies for tackling complicated tumor treatments like drug resistance.In this work,we have generated a therapeutic cisplatin-crosslinked albumin hydrogel(BC-Gel)that allows the local release of L-Buthionine-sulfoximine(BSO),cisplatin,and glucose oxidase(GOx)with distinct release kinetics.The BC-Gel with favorable biostimuli degradability and injectability could release therapeutic agents in a programmed manner within the tumor microenvironment(TME).The preferentially released BSO significantly suppressed the glutathione(GSH)-related cisplatin resistance and sensitized the tumor cells to cisplatin by inhibiting theγ-glutamylcysteine synthetase.Meanwhile,cisplatin achieved a sequential release and long-term treatment following the bioresponsive gel degradation under the combined action of chloride ions(Cl−)and proteinase in the body.In addition,the overproduced H_(2)O_(2)of GOx-catalyzed glucose oxidation accelerated the depletion of existed GSH within cells and further weakened the cisplatin resistance,achieving enhanced tumor treatment together with a strong cell-killing effect.The above sequential drug release strategy based on the dual GSH depletion effect breaks the balance of the GSH-mediated redox TME and enhances the sensitivity of A549 cells to cisplatin forcefully,and provides a promising way for temporal control of drug release as well as efficient cancer combination therapy.

A DNA Nano-train Carrying a Predefined Drug Combination for Cancer Therapy

Herein,we reported a tumor cell-targeting aptamer-nano-train to deliver paclitaxel(PTX)and combretastatin A4(CA4)at a predefined ratio to cancer cells based on DNA nanotechnology.Such a drug-carrying aptamer-nano-train(aptamer-NT-PTX/CA4)was prepared via self-assembly of two DNA hairpins,which were conjugated with PTX and CA4,respectively,induced by aptamer trigger.Our research revealed that the aptamer-NT-PTX/CA4 could specifically recognize CD71-positive cancer cells,but not CD71-negative healthy normal cells,and achieve synergistic therapeutic effect on cancer cells.The aptamer-nano-train-based strategy is simple and efficient,and provides a new platform for drug combination cancer therapy.

Theraputic Effect on Carboplatin and Etoposide Combinative Therapy on 123 Lung Cancer Cases.

The clinical effcct of Carboplatin and Etoposide (CE regimen) on 58 cases of small cell lung cancer (SCLC) and 65

Tetrahedron DNA nanostructure/iron-based nanomaterials for combined tumor therapy

Triple-negative breast cancer,due to its aggressive nature and lack of targeted treatment,faces serious challenges in breast cancer treatment.Conventional therapies,such as chemotherapy,are encumbered by a range of limitations,and there is an urgent need for more effective treatment strategies.Ferroptosis,as an iron-dependent form of cell death,has exhibited promising potential in cancer treatment.Combining ferroptosis with other cancer therapies offers new avenues for treatment.Tetrahedral DNA nanostructure(TDN),a novel DNA-based three-dimensional(3D)nanomaterial,is promising drug delivery vehicle and can be utilized for functionalizing inorganic nanomaterials.In this work,we have demonstrated the preparation of Fe_(3)O_(4)-PEI@TDN-DOX nanocomposites and elucidated their antitumor mechanism.The TDN facilitated the enhanced cellular uptake of polyetherimide(PEI)-modified Fe_(3)O_(4),and the delivery of the chemotherapeutic drug doxorubicin(DOX)further augmented their anti-tumor effect.This novel strategy can destroy the tumor redox homeostasis and produce overwhelming lipid peroxides,consequently sensitizing the tumor to ferroptosis.The integration of ferroptosis with other cancer therapies opens up new possibilities for treatment.This research provides valuable mechanistic insights and practical strategies for leveraging nanotechnology to induce ferroptosis and amplify its impact on tumor cells.

Anti-tumor effects of combined doxorubicin and siRNA for pulmonary delivery

Direct administration of drugs and genes to the lungs by pulmonary delivery offers a potential effective therapy for lung cancers.In this study,combined doxorubicin（DOX） and Bcl2 siRNA was employed for cancer therapy using polyethylenimine（PEI） as the carrier of Bcl2 siRNA.Most of the DOX and siRNA possessed high cellular uptake efficiency in B16F10 cells,which was proved by FCM and CLSM analysis.Real-time PCR showed that PEI/Bcl2 siRNA exhibited high gene silencing efficiency with 70%Bcl2 mRNA being knocked down.The combination of DOX and siRNA could enhance the cell proliferation inhibition and the cell apoptosis against B16F10 cells compared to free DOX or PEI/Bcl2 siRNA.Furthermore,the biodistribution of DOX and siRNA via pulmonary administration was studied in mice with B16F10 metastatic lung cancer.The results showed that most of the DOX and siRNA were accumulated in lungs and lasted at least for 3 days,which suggested that combined DOX and siRNA by pulmonary administration may have high anti-tumor effects for metastatic lung cancer treatment in vivo.