Nanomedicine-enabled chemotherapy-based synergetic cancer treatments

AbstractChemotherapy remains one of the most prevailing regimens hitherto in the fight against cancer, but its development has been being suffering from various fatal side effects associated with the non-specific toxicity of common chemical drugs. Advances in biomedical application of nanomedicine have been providing alternative but promising approaches for cancer therapy, by leveraging its excellent intrinsic physicochemical properties to address these critical concerns. In particular, nanomedicine-enabled chemotherapy has been established as a safer and promising therapeutic modality, especially the recently proposed nanocatalytic medicine featuring the capabilities to generate toxic substances by initiating diverse catalytic reactions within the tumor without directly relying on highly toxic but non-selective chemotherapeutic agents. Of special note, under exogenous/endogenous stimulations, nanomedicine can serve as a versatile platform that allows additional therapeutic modalities (photothermal therapy (PTT), photodynamic therapy (PDT), chemodynamic therapy (CDT), etc.) to be seamlessly integrated with chemotherapy for efficacious synergistic treatments of tumors. Here, we comprehensively review and summarize the representative studies of multimodal synergistic cancer treatments derived from nanomedicine and nanocatalytic medicine-enabled chemotherapy in recent years, and their underlying mechanisms are also presented in detail. A number of existing challenges and further perspectives for nanomedicine-synergized chemotherapy for malignant solid tumor treatments are also highlighted for understanding this booming research area as comprehensively as possible. Graphical Abstract

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Low-Temperature Photothermal Therapy: Strategies and Applications

Research ◽

10.34133/2021/9816594 ◽

2021 ◽

Vol 2021 ◽

pp. 1-38

Author(s):

Xiulin Yi ◽

Qiu-Yi Duan ◽

Fu-Gen Wu

Keyword(s):

Low Temperature ◽

Photothermal Therapy ◽

Combined Treatments ◽

Excellent Performance ◽

Cancer Treatments ◽

Future Directions ◽

Excessive Heat ◽

Therapeutic Modalities ◽

Therapy Strategies ◽

Mild Temperature

Although photothermal therapy (PTT) with the assistance of nanotechnology has been considered as an indispensable strategy in the biomedical field, it still encounters some severe problems that need to be solved. Excessive heat can induce treated cells to develop thermal resistance, and thus, the efficacy of PTT may be dramatically decreased. In the meantime, the uncontrollable diffusion of heat can pose a threat to the surrounding healthy tissues. Recently, low-temperature PTT (also known as mild PTT or mild-temperature PTT) has demonstrated its remarkable capacity of conquering these obstacles and has shown excellent performance in bacterial elimination, wound healing, and cancer treatments. Herein, we summarize the recently proposed strategies for achieving low-temperature PTT based on nanomaterials and introduce the synthesis, characteristics, and applications of these nanoplatforms. Additionally, the combination of PTT and other therapeutic modalities for defeating cancers and the synergistic cancer therapeutic effect of the combined treatments are discussed. Finally, the current limitations and future directions are proposed for inspiring more researchers to make contributions to promoting low-temperature PTT toward more successful preclinical and clinical disease treatments.

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Innovations in superficial bladder cancer treatments. Review

Urologia Journal ◽

10.1177/039156030707400302 ◽

2007 ◽

Vol 74 (3) ◽

pp. 133-138 ◽

Cited By ~ 1

Author(s):

M. Racioppi ◽

A. Volpe ◽

R. Falabella ◽

E. Cappa ◽

D. D'Agostino ◽

...

Keyword(s):

Bladder Cancer ◽

Superficial Bladder Cancer ◽

Multimodality Treatment ◽

Complete Removal ◽

Chemotherapeutic Agents ◽

Intravesical Instillation ◽

Cancer Treatments ◽

Therapeutic Modalities ◽

Clinical Investigations ◽

Tumor Prevention

Bladder cancer treatment is a challenge for both urologists and oncologists. Particularly during these last years many changes have been made in the management of superficial bladder cancer. In the case of superficial bladder cancer, intravesical instillation of chemo/immunotherapeutic agents after transurethral resection is the standard. The treatment goals include: complete removal of the initial tumor, prevention of recurrences and inhibition of disease progression. This work aims at reviewing the new developments in the therapeutic field of superficial bladder cancer. A growing trend involves the use of multimodality treatment to obtain the activation of the host immunity against the tumor, and to enhance the cytotoxic effects of chemotherapeutic agents. The new therapeutic modalities, which are under preclinical and clinical investigations, are showing promising results.

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Dysregulation of DNA methylation during development as a potential mechanisms contributing to obsessive compulsive disorders and autism

10.31234/osf.io/udfya ◽

2019 ◽

Author(s):

German I. Todorov ◽

Karthikeyan Mayilvahanan ◽

David Ashurov ◽

Catarina Cunha

Keyword(s):

Mouse Model ◽

Autism Spectrum ◽

Obsessive Compulsive ◽

Cancer Treatments ◽

Knock Out ◽

Treatment Priority ◽

Underlying Mechanisms ◽

Knock Out Mice ◽

Obsessive Compulsive Disorders ◽

Compulsive Disorders

Autism Spectrum Disorder (ASD) is a pervasive developmental disorder, that is raising at a concerning rate. However, underlying mechanisms are still to be discovered. Obsessions and compulsions are the most debilitating aspect of these disorders (OCD), and they are the treatment priority for patients. SAPAP3 knock out mice present a reliable mouse model for repetitive compulsive behavior and are mechanistically closely related to the ASD mouse model Shank3 on a molecular level and AMPA receptor net effect. The phenotype of SAPAP3 knock out mice is obsessive grooming that leads to self-inflicted lesions by 4 months of age. Recent studies have accumulated evidence, that epigenetic mechanisms are important effectors in psychiatric conditions such as ASD and OCD. Methylation is the most studied mechanism, that recently lead to drug developments for more precise cancer treatments. We injected SAPAP3 mice with an epigenetic demethylation drug RG108 during pregnancy and delayed the onset of the phenotype in the offspring by 4 months. This result gives us clues about possible mechanism involved in OCD and ASD. Additionally, it shows that modulation of methylation mechanisms during development might be explored as a preventative treatment in the cases of high inherited risk of certain mental health conditions.

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A Comprehensive Review on Nanotechnology-Based Innovations in Topical Drug Delivery for the Treatment of Skin Cancer

Current Pharmaceutical Design ◽

10.2174/1381612826666200819202821 ◽

2020 ◽

Vol 26 (44) ◽

pp. 5720-5731 ◽

Cited By ~ 1

Author(s):

Arun Singh Lalotra ◽

Vishesh Singh ◽

Bharat Khurana ◽

Shelly Agrawal ◽

Shubham Shrestha ◽

...

Keyword(s):

Skin Cancer ◽

Cell Carcinoma ◽

Systemic Exposure ◽

Chemotherapeutic Agents ◽

The Body ◽

Toxic Substances ◽

Abnormal Growth ◽

Dermal Layer ◽

Therapeutic Benefits ◽

Carrier Systems

Background: Skin is the largest organ of the body and helps to regulate several physiological functions. It acts as a barrier that protects the body against UV-radiation, toxic substances, infections, etc. The abnormal growth of the skin cells is called skin cancer. Different types of skin cancer can be classified as Basal Cell Carcinoma (BCC) and Squamous Cell Carcinoma (SCC); which mainly occur due to chronic exposure to UV- sunlight and pollution. Methods: The conventional topical treatments of skin cancer such as cream, gel, ointment, etc., are more occlusive and thus they do not penetrate deep into the skin (dermal layer) and remain at the upper part of the skin (epidermal layer). The stratum corneum acts as a physiological barrier for the drug-loaded in the conventional formulation. The novel carrier systems have the potential to facilitate the penetration of the drug deep into the skin (dermal layer) because these have less size and higher flexibility than conventional treatment. Conclusion: In the present review, we have discussed various novel carrier systems being investigated for the topical application of chemotherapeutic agents for efficient skin targeting and better dermatological as well as therapeutic benefits with minimal systemic exposure and toxicity.

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Melatonin as an Adjuvant to Antiangiogenic Cancer Treatments

Cancers ◽

10.3390/cancers13133263 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3263

Author(s):

Alicia González ◽

Carolina Alonso-González ◽

Alicia González-González ◽

Javier Menéndez-Menéndez ◽

Samuel Cos ◽

...

Keyword(s):

Synergistic Effect ◽

Protective Effect ◽

Cancer Cells ◽

Tumor Cells ◽

Chemotherapeutic Agents ◽

Inhibitory Effects ◽

Anticancer Effect ◽

Cancer Treatments ◽

Melatonin Administration ◽

Effects Of Radiation

Melatonin is a hormone with different functions, antitumor actions being one of the most studied. Among its antitumor mechanisms is its ability to inhibit angiogenesis. Melatonin shows antiangiogenic effects in several types of tumors. Combination of melatonin and chemotherapeutic agents have a synergistic effect inhibiting angiogenesis. One of the undesirable effects of chemotherapy is the induction of pro-angiogenic factors, whilst the addition of melatonin is able to overcome these undesirable effects. This protective effect of the pineal hormone against angiogenesis might be one of the mechanisms underlying its anticancer effect, explaining, at least in part, why melatonin administration increases the sensitivity of tumors to the inhibitory effects exerted by ordinary chemotherapeutic agents. Melatonin has the ability to turn cancer totally resistant to chemotherapeutic agents into a more sensitive chemotherapy state. Definitely, melatonin regulates the expression and/or activity of many factors involved in angiogenesis which levels are affected (either positively or negatively) by chemotherapeutic agents. In addition, the pineal hormone has been proposed as a radiosensitizer, increasing the oncostatic effects of radiation on tumor cells. This review serves as a synopsis of the interaction between melatonin and angiogenesis, and we will outline some antiangiogenic mechanisms through which melatonin sensitizes cancer cells to treatments, such as radiotherapy or chemotherapy.

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Finding an easy way to harmonize: a review of advances in clinical research and combination strategies of EZH2 inhibitors

Clinical Epigenetics ◽

10.1186/s13148-021-01045-1 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Chen Li ◽

Yan Wang ◽

Yueqing Gong ◽

Tengrui Zhang ◽

Jiaqi Huang ◽

...

Keyword(s):

Treatment Modalities ◽

Preclinical Studies ◽

Combination Therapies ◽

Tumor Treatment ◽

Antitumor Effects ◽

Therapeutic Modalities ◽

Combination Strategies ◽

Anti Cancer ◽

Underlying Mechanisms ◽

The Individual

AbstractEnhancer of zeste homolog 2 inhibitors (EZH2i) have garnered increased attention owing to their anticancer activity by targeting EZH2, a well-known cancer-promoting factor. However, some lymphomas are resistant to EZH2i, and EZH2i treatment alone is ineffective in case of EZH2-overexpressing solid tumors. The anti-cancer efficacy of EZH2i may be improved through safe and effective combinations of these drugs with other treatment modalities. Preclinical evidence indicates that combining EZH2i with other therapies, such as immunotherapy, chemotherapy, targeted therapy, and endocrine therapy, has complementary or synergistic antitumor effects. Therefore, elucidating the underlying mechanisms of the individual constituents of the combination therapies is fundamental for their clinical application. In this review, we have summarized notable clinical trials and preclinical studies using EZH2i, their progress, and combinations of EZH2i with different therapeutic modalities, aiming to provide new insights for tumor treatment.

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Approach to the Febrile Patient with No Obvious Focus of Infection

Pediatrics in Review ◽

10.1542/pir.5.10.305 ◽

1984 ◽

Vol 5 (10) ◽

pp. 305-315

Author(s):

Sarah S. Long

Keyword(s):

Antimicrobial Agents ◽

Group B Streptococcus ◽

Invasive Disease ◽

Chemotherapeutic Agents ◽

The Body ◽

Therapeutic Modalities ◽

Body Of Knowledge ◽

Age Related ◽

Focus Of Infection ◽

Group B

The summary in Table 1 could be used as a mental checklist for the pediatrician who examines a child with fever. Whether the pediatrician opts to "keep the rules" or appropriately decides to "break the rules," knowledge of the guidelines will help him to focus his approach and to adopt attitudes of caution in certain circumstances. The body of knowledge of infectious agents chemotherapeutic agents has burgeoned over the past 40 years; the rules have changed very little. Thus, the rules might also serve as standards against which "new discoveries" that dictate departure from an established mode of clinical practice would have to be weighed. The adage, "Name the bug before you choose a drug," is especially germaine to pediatrics. Potential pathogens or "bugs" continually change as the patient's age, exposure, and immunity change. The serious diseases they cause mandate that initial treatment be given with the best "drugs." The age-related causes of bacterial meningitis presented in Table 2 could serve as a primer for age-related causes of other invasive disease as well. For bone, joint, and soft tissue infection as well as for septicemia without a focus the age line for group B Streptococcus and H influenzae would be extended upward and S aureus would be added for all ages. Although the relative importance of each pathogen for each clinical entity might vary, therapeutic considerations would be appropriately served by a schema such as this. Unfortunately, the susceptibility of pathogens to antimicrobial agents will continue to change. Fortunately, new and potentially better therapeutic agents will continue to be discovered or invented. When new problems of antibiotic resistance emerge or when superior therapeutic modalities are proved, the pediatrician must be knowledgeable of such events and be prepared for change.

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Live-cell imaging shows uneven segregation of extrachromosomal DNA elements and transcriptionally active extrachromosomal DNA clusters in cancer

10.1101/2020.10.20.335216 ◽

2020 ◽

Author(s):

Eunhee Yi ◽

Amit D. Gujar ◽

Molly Guthrie ◽

Hoon Kim ◽

Kevin C. Johnson ◽

...

Keyword(s):

Rna Polymerase Ii ◽

Live Cell Imaging ◽

Direct Evidence ◽

Extrachromosomal Dna ◽

Cancer Treatments ◽

Fluorescent Markers ◽

Copy Numbers ◽

Dna Elements ◽

Underlying Mechanisms

AbstractOncogenic extrachromosomal DNA elements (ecDNAs) promote intratumoral heterogeneity, creating a barrier for successful cancer treatments. The underlying mechanisms are poorly understood and studies are hampered in part by a lack of adequate tools enabling studies of ecDNA behavior. Here, we show that single-cell ecDNA copy numbers follow a Gaussian distribution across tumor cells in vitro and in patient glioblastoma specimens, suggesting uneven ecDNA segregation during mitosis. We established a CRISPR-based approach which leverages unique ecDNA breakpoint sequences to tag ecDNA with fluorescent markers in living cells. Applying this method during mitosis revealed disjointed ecDNA inheritance patterns, providing an explanation for rapid ecDNA accumulation in cancer. Post-mitosis, ecDNAs tended to cluster and clustered ecDNAs colocalized with RNA polymerase II, promoting transcription of cargo oncogenes. Our observations provide direct evidence for uneven segregation of ecDNA and shed new lights of mechanisms through which ecDNAs contribute to oncogenesis.

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Curcumin Enhanced Busulfan-Induced Apoptosis through Downregulating the Expression of Survivin in Leukemia Stem-Like KG1a Cells

BioMed Research International ◽

10.1155/2015/630397 ◽

2015 ◽

Vol 2015 ◽

pp. 1-16 ◽

Cited By ~ 11

Author(s):

Guangyang Weng ◽

Yingjian Zeng ◽

Jingya Huang ◽

Jiaxin Fan ◽

Kunyuan Guo

Keyword(s):

Specific Inhibitor ◽

Annexin V ◽

Chemotherapeutic Agents ◽

Combination Group ◽

Hematopoietic Stem ◽

Leukemia Relapse ◽

Conditioning Regimens ◽

Underlying Mechanisms ◽

Induced Apoptosis ◽

Related Proteins

Leukemia relapse and nonrecurrence mortality (NRM) due to leukemia stem cells (LSCs) represent major problems following hematopoietic stem cell transplantation (HSCT). To eliminate LSCs, the sensitivity of LSCs to chemotherapeutic agents used in conditioning regimens should be enhanced. Curcumin (CUR) has received considerable attention as a result of its anticancer activity in leukemia and solid tumors. In this study, we investigated the cytotoxic effects and underlying mechanisms in leukemia stem-like KG1a cells exposed to busulfan (BUS) and CUR, either alone or in combination. KG1a cells exhibiting BUS-resistance demonstrated by MTT and annexin V/propidium iodide (PI) assays, compared with HL-60 cells. CUR induced cell growth inhibition and apoptosis in KG1a cells. Apoptosis of KG1a cells was significantly enhanced by treatment with CUR+BUS, compared with either agent alone. CUR synergistically enhanced the cytotoxic effect of BUS. Seven apoptosis-related proteins were modulated in CUR- and CUR+BUS-treated cells analyzed by proteins array analysis. Importantly, the antiapoptosis protein survivin was significantly downregulated, especially in combination group. Suppression of survivin with specific inhibitor YM155 significantly increased the susceptibility of KG1a cells to BUS. These results demonstrated that CUR could increase the sensitivity of leukemia stem-like KG1a cells to BUS by downregulating the expression of survivin.

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Nanomaterials for Targeted Delivery of Anticancer Drugs: An Overview

Current Nanomaterials ◽

10.2174/2405461506666210119095130 ◽

2021 ◽

Vol 06 ◽

Author(s):

Bhavna Choudhary ◽

Pubalee Sarmah

Keyword(s):

Drug Delivery ◽

Targeted Delivery ◽

Chemotherapeutic Agents ◽

Cancer Drug ◽

Cancer Treatments ◽

Area Of Interest ◽

Efficient Delivery ◽

Delivery Vehicles ◽

Materials Used ◽

Developing Area

: Application of nanomaterials in drug delivery is a rapidly developing area of interest. The main intention in the development of these drug delivery vehicles is to successfully know the targeted delivery-related efforts and carrying drugs to the required sites of therapeutic action with reduction in adverse side effects. The task for targeted drug delivery to reach pathological are-as has increased advances in nanomedicine. But the high toxicity of uncoated nanoparticles restricts the use in humans. So, to reduce toxicity, the encapsulation of nanoparticles is done with bio compatible materials. There are many efficient delivery systems thathave been developed in which nanoparticles are loaded with the cancer drug involvingbi-layer molecules. The ﬁelds of nanotechnology has always played a crucial role in electronics, biology and medicine. Its application can be ap-praised, as it involves the materials to be designed at atomic and molecular level.This article reviews different types of nano- materials used as delivery vehicles for chemotherapeutic agents and their mechanism of action that improve the therapeutic efficacy of the drugs. The recent scientiﬁc advances in the area of chemotherapy are also discussed with emphasizingthe fu-ture prospects in cancer treatments.

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