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Small (Weinheim An Der Bergstrasse,... Oct 2023Immunotherapy gains increasing focus in treating triple-negative breast cancer (TNBC), while its efficacy is greatly restricted owing to low tumor immunogenicity and...
Immunotherapy gains increasing focus in treating triple-negative breast cancer (TNBC), while its efficacy is greatly restricted owing to low tumor immunogenicity and immunosuppressive tumor microenvironment (ITM). Herein, a LyP-1 and chondroitin sulfate (CS) dual-modified liposome co-loaded with paclitaxel (PTX) and cryptotanshinone (CTS), namely CS/LyP-1-PC Lip, is engineered for TNBC chemoimmunotherapy via induction of immunogenic cell death (ICD) and inhibition of signal transducer and activator of transcript-3 (STAT3) activation. CS/LyP-1-PC Lip enhances cellular uptake through p32 and CD44 dual receptor-mediated endocytosis. Within the tumor, the CS layer is continuously detached by hyaluronidase to release drugs. Subsequently, CTS sensitizes the cytotoxicity of PTX to 4T1 tumor cells. PTX induces ICD of tumor cells and facilitates infiltration of cytotoxic T lymphocyte to provoke immune response. Meanwhile, the concomitant delivery of CTS inhibits STAT3 activation to decrease infiltration of regulatory T cell, M2-type tumor-associated macrophage, and myeloid-derived suppressor cell, thus reversing ITM. Markedly, the dual-targeting liposome shows superior anti-tumor efficacy in subcutaneous TNBC mice and significant lung metastasis suppression in tumor metastasis model. Overall, this work offers a feasible combination regimen and a promising nanoplatform for the development of TNBC chemoimmunotherapy.
Topics: Humans; Animals; Mice; Liposomes; Triple Negative Breast Neoplasms; Immunogenic Cell Death; Cell Line, Tumor; Paclitaxel; Immunotherapy; Tumor Microenvironment; STAT3 Transcription Factor
PubMed: 37264710
DOI: 10.1002/smll.202302834 -
Environmental Research Dec 2023The site-specific delivery of drugs, especially anti-cancer drugs has been an interesting field for researchers and the reason is low accumulation of cytotoxic drugs in... (Review)
Review
The site-specific delivery of drugs, especially anti-cancer drugs has been an interesting field for researchers and the reason is low accumulation of cytotoxic drugs in cancer cells. Although combination cancer therapy has been beneficial in providing cancer drug sensitivity, targeted delivery of drugs appears to be more efficient. One of the safe, biocompatible and efficient nano-scale delivery systems in anti-cancer drug delivery is liposomes. Their particle size is small and they have other properties such as adjustable physico-chemical properties, ease of functionalization and high entrapment efficiency. Cisplatin is a chemotherapy drug with clinical approval in patients, but its accumulation in cancer cells is low due to lack of targeted delivery and repeated administration results in resistance development. Gene and drug co-administration along with cisplatin/paclitaxel have resulted in increased sensitivity in tumor cells, but there is still space for more progress in cancer therapy. The delivery of cisplatin/paclitaxel by liposomes increases accumulation of drug in tumor cells and impairs activity of efflux pumps in promoting cytotoxicity. Moreover, phototherapy along with cisplatin/paclitaxel delivery can increase potential in tumor suppression. Smart nanoparticles including pH-sensitive nanoparticles provide site-specific delivery of cisplatin/paclitaxel. The functionalization of liposomes can be performed by ligands to increase targetability towards tumor cells in mediating site-specific delivery of cisplatin/paclitaxel. Finally, liposomes can mediate co-delivery of cisplatin/paclitaxel with drugs or genes in potentiating tumor suppression. Since drug resistance has caused therapy failure in cancer patients, and cisplatin/paclitaxel are among popular chemotherapy drugs, delivery of these drugs mediates targeted suppression of cancers and prevents development of drug resistance. Because of biocompatibility and safety of liposomes, they are currently used in clinical trials for treatment of cancer patients. In future, the optimal dose of using liposomes and optimal concentration of loading cisplatin/paclitaxel on liposomal nanocarriers in clinical trials should be determined.
Topics: Humans; Liposomes; Cisplatin; Paclitaxel; Antineoplastic Agents; Drug Delivery Systems; Neoplasms; Cell Line, Tumor
PubMed: 37734579
DOI: 10.1016/j.envres.2023.117111 -
Frontiers in Bioengineering and... 2023The incidence and mortality of cancer are gradually increasing. The highly invasive and metastasis of tumor cells increase the difficulty of diagnosis and treatment, so... (Review)
Review
The incidence and mortality of cancer are gradually increasing. The highly invasive and metastasis of tumor cells increase the difficulty of diagnosis and treatment, so people pay more and more attention to the diagnosis and treatment of cancer. Conventional treatment methods, including surgery, radiotherapy and chemotherapy, are difficult to eliminate tumor cells completely. And the emergence of nanotechnology has boosted the efficiency of tumor diagnosis and therapy. Herein, the research progress of nanotechnology used for tumor diagnosis and treatment is reviewed, and the emerging detection technology and the application of nanodrugs in clinic are summarized and prospected. The first part refers to the application of different nanomaterials for imaging and detection , which includes magnetic resonance imaging, fluorescence imaging, photoacoustic imaging and biomarker detection. The distinctive physical and chemical advantages of nanomaterials can improve the detection sensitivity and accuracy to achieve tumor detection in early stage. The second part is about the nanodrug used in clinic for tumor treatment. Nanomaterials have been widely used as drug carriers, including the albumin paclitaxel, liposome drugs, mRNA-LNP, protein nanocages, micelles, membrane nanocomplexes, microspheres et al., which could improve the drug accumulate in tumor tissue through enhanced permeability and retention effect to kill tumor cells with high efficiency. But there are still some challenges to revolutionize traditional tumor diagnosis and anti-drug resistance based on nanotechnology.
PubMed: 37576984
DOI: 10.3389/fbioe.2023.1249875 -
Journal of Controlled Release :... Nov 2023It is time for the story of mitochondria and intracellular communication in multidrug resistant cancer to be rewritten. Herein we characterize the extent and cellular...
It is time for the story of mitochondria and intracellular communication in multidrug resistant cancer to be rewritten. Herein we characterize the extent and cellular advantages of mitochondrial network fusion in multidrug resistant (MDR) breast cancer and have designed a novel nanomedicine that disrupts mitochondrial network fusion and systematically manipulates organelle fusion and function. Combination Organelle Mitochondrial Endoplasmic reticulum Therapy (COMET) is an innovative translational nanomedicine for treating MDR triple negative breast cancer (TNBC) that has superior safety and equivalent efficacy to the current standard of care (paclitaxel). Our study has demonstrated that the increased mitochondrial networks in MDR TNBC contribute to apoptotic resistance and network fusion is mediated by mitofusin2 (MFN2) on the outer mitochondrial membrane. COMET consists of three components; Mitochondrial Network Disrupting (MiND) nanoparticles (NPs) that are loaded with an anti-MFN2 peptide, tunicamycin, and Bam7. The therapeutic rationale of COMET is to reduce the apoptotic threshold in MDR cells with MiND NPs, followed by inducing the endoplasmic reticulum mediated unfolded protein response (UPR) by stressing MDR cells with tunicamycin, and finally, directly inducing mitochondrial apoptosis with Bam7 which is a specific bcl-2 Bax activator. MiND NPs are PEGylated liposomes with the 21 amino acid (2577.98 MW) anti-MFN2 peptide compartmentalized in the aqueous core. Hypoxia (0.5% oxygen) was used to create MDR derivatives of MDA-MB-231 cells and BT-549 cells. Mitochondrial networks were quantified using 3D analysis of 60× live cell images acquired with a Keyence BZ-X710 microscope and MiND NPs effectively fragmented mitochondrial networks in drug sensitive and MDR TNBC cells. The IC values, combination index, and dose reduction index derived from dose response studies demonstrate that MiND NPs decrease the apoptotic threshold of both drug sensitive and MDR TNBC cells and COMET is a synergistic drug combination. Complex V (ATP synthase) extracted from bovine cardiac mitochondria was used to assess the effect of MiND NPs on OXPHOS; both MiND NPs and anti-MFN2 peptide solution significantly decrease the activity of mitochondrial complex V and decrease the capacity of OXPHOS. A BacMam viral vector based fluorescent biosensor was used to quantify the unfolded protein response (UPR) at the level of the endoplasmic reticulum and tunicamycin specifically induces the UPR in drug sensitive and MDR TNBC cells. A caspase 3 colorimetric assay demonstrated that the synergistic triple drug combination of COMET increases the ability of Bam7 to specifically induce apoptosis. Dose limiting toxicity and off target effects are a significant challenge for current chemotherapy regimens including paclitaxel. COMET has significantly lower cytotoxicity than paclitaxel in human embryonic kidney epithelial cells and has the potential to fulfill the clinical need for safer cancer therapeutics. COMET is a promising early stage translational nanomedicine for treating MDR TNBC. Manipulating intracellular communication and organelle fusion is a novel approach to treating MDR cancer. The data from this study has rewritten the story of mitochondria, organelle fusion, and intracellular communication and by targeting this intersection, COMET is an exciting new chapter in cancer therapeutics that could transform the clinical outcome of MDR TNBC.
Topics: Animals; Cattle; Humans; Drug Resistance, Multiple; Triple Negative Breast Neoplasms; Tunicamycin; Drug Resistance, Neoplasm; Paclitaxel; Mitochondria; Apoptosis; Endoplasmic Reticulum; Peptides; Drug Combinations; Cell Line, Tumor
PubMed: 37717658
DOI: 10.1016/j.jconrel.2023.09.023 -
AAPS PharmSciTech Apr 2024Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease that has been well-reported in the medical literature. Its incidence has... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease that has been well-reported in the medical literature. Its incidence has risen, particularly in light of the recent COVID-19 pandemic. Conventionally, IPF is treated with antifibrotic drugs-pirfenidone and nintedanib-along with other drugs for symptomatic treatments, including corticosteroids, immunosuppressants, and bronchodilators based on individual requirements. Several drugs and biologicals such as fluorofenidone, thymoquinone, amikacin, paclitaxel nifuroxazide, STAT3, and siRNA have recently been evaluated for IPF treatment that reduces collagen formation and cell proliferation in the lung. There has been a great deal of research into various treatment options for pulmonary fibrosis using advanced delivery systems such as liposomal-based nanocarriers, chitosan nanoparticles, PLGA nanoparticles, solid lipid nanocarriers, and other nanoformulations such as metal nanoparticles, nanocrystals, cubosomes, magnetic nanospheres, and polymeric micelles. Several clinical trials are also ongoing for advanced IPF treatments. This article elaborates on the pathophysiology of IPF, its risk factors, and different advanced drug delivery systems for treating IPF. Although extensive preclinical data is available for these delivery systems, the clinical performance and scale-up studies would decide their commercial translation.
Topics: Humans; Pandemics; Idiopathic Pulmonary Fibrosis; Lung; Drug Delivery Systems; Pyridones; Nanoparticles
PubMed: 38589751
DOI: 10.1208/s12249-024-02793-y -
Frontiers in Bioengineering and... 2023Nowadays, it is still quite difficult to combat glioblastoma, which is one of the most lethal cancers for human beings. Combinatory therapy, which could not only improve...
Light-activatable and hyperthermia-sensitive "all-in-one" theranostics: NIR-II fluorescence imaging and chemo-photothermal therapy of subcutaneous glioblastoma by temperature-sensitive liposome-containing AIEgens and paclitaxel.
Nowadays, it is still quite difficult to combat glioblastoma, which is one of the most lethal cancers for human beings. Combinatory therapy, which could not only improve therapeutic efficacy and overcome multiple drug resistance but also decrease the threshold therapeutic drug dosage and minimize side effects, would be an appealing candidate for glioblastoma treatment. Herein, we report fluorescence imaging in the second near-infrared window (NIR-II)-guided combinatory photothermal therapy (PTT) and chemotherapy of glioblastoma with a newly formulated nanomedicine termed . It is composed of temperature-sensitive liposome (TSL) carriers, NIR-II emissive and photothermal aggregation-induced emission (AIE) dyes, and chemotherapeutic paclitaxel (PTX) as well. shows spherical morphology with diameters of approximately 55 and 85 nm by transmission electron microscopy and laser light scattering, respectively, a zeta potential of -14.83 mV, good stability in both size and photoactivity, strong light absorption with a peak of approximately 770 nm, and bright emission from 900 nm to 1,200 nm. After excitation with an 808-nm laser with good spatiotemporal controllability, emits bright NIR-II fluorescence signals for tumor diagnosis , exhibits high photothermal conversion efficiency (68.8%), and triggers drug release of PTX under hypothermia, which assists in efficient tumor ablation and . This research demonstrates that "all-in-one" theranostics with NIR-II fluorescence imaging-guided combinatory PTT and chemotherapy is an efficient treatment paradigm for improving the prognosis of brain cancers.
PubMed: 38213575
DOI: 10.3389/fbioe.2023.1343694 -
Journal of Materials Chemistry. B Sep 2023Photodynamic therapy is an effective method for the treatment of several types of cancerous and noncancerous diseases. The key to the success of this treatment method is... (Review)
Review
Photodynamic therapy is an effective method for the treatment of several types of cancerous and noncancerous diseases. The key to the success of this treatment method is effective drug delivery to the site of action, for instance, a tumor. This ensures not only the high effectiveness of the therapy but also the suppression of side effects. But how to achieve effective targeted delivery? Lately, much attention has been paid to systems based on the so-called Trojan horse model, which is gaining increasing popularity. The principle of this model is that the effective drug is hidden in the internal structure of a nanoparticle, liposome, or nanoemulsion and is released only at the site of action. In this review article, we focus on drugs from the group of mitotic poisons, taxanes, and their use with photosensitizers in combined therapy. Here, we discuss the possibilities of how to improve the paclitaxel and docetaxel bioavailability, as well as their specific targeting for use in combined photo- and chemotherapy. Moreover, we also present the state of the art multifunctional drugs based on cabazitaxel which, owing to a suitable combination with photosensitizers, can be used besides photodynamic therapy and also in photoacoustic imaging or sonodynamic therapy.
Topics: Photosensitizing Agents; Photochemotherapy; Drug Delivery Systems; Taxoids; Paclitaxel
PubMed: 37615658
DOI: 10.1039/d2tb02147a -
Journal of Oncology Pharmacy Practice :... Mar 2024Paclitaxel is an effective chemotherapeutic agent against a variety of cancer types. However, the clinical utility of paclitaxel is restricted by its poor solubility in... (Review)
Review
PURPOSE
Paclitaxel is an effective chemotherapeutic agent against a variety of cancer types. However, the clinical utility of paclitaxel is restricted by its poor solubility in water and high toxicity, resulting in low drug tolerance. These difficulties could be resolved by using suitable pharmacological carriers. Hence, it is essential to determine innovative methods of administering this effective medication to overcome paclitaxel's inherent limitations.
METHODS
An extensive literature search was conducted using multiple electronic databases to identify relevant studies published.
RESULTS
In this comprehensive analysis, many different paclitaxel delivery systems are covered and discussed, such as albumin-bound paclitaxel, polymeric micelles, paclitaxel-loaded liposomes, prodrugs, cyclodextrins, and peptide-taxane conjugates. Moreover, the review also covers various delivery routes of conventional paclitaxel or novel paclitaxel formulations, such as oral administration, local applications, and intraperitoneal delivery.
CONCLUSION
In addition to albumin-bound paclitaxel, polymeric micelles appear to be the most promising formulations for innovative drug delivery systems at present. A variety of variants of polymeric micelles are currently undergoing advanced phases of clinical trials.
Topics: Humans; Micelles; Antineoplastic Agents, Phytogenic; Albumin-Bound Paclitaxel; Paclitaxel; Drug Delivery Systems; Polymers; Drug Carriers
PubMed: 38204196
DOI: 10.1177/10781552231208978 -
Urologic Oncology Apr 2024Nanocarriers (NCs) are a form of nanotechnology widely investigated in cancer treatment to improve the safety and efficacy of systemic therapies by increasing tumor... (Review)
Review
Nanocarriers (NCs) are a form of nanotechnology widely investigated in cancer treatment to improve the safety and efficacy of systemic therapies by increasing tumor specificity. Numerous clinical trials have explored the use of NCs in urologic cancers since the approval of the first NCs for cancer treatment over 20 years ago. The objective of this systematic review is to examine the effectiveness and safety of NCs in treating urological cancers. This paper summarizes the state of the field by investigating peer-reviewed, published results from 43 clinical trials involving the use of NCs in bladder, prostate, and kidney cancer patients with a focus on safety and efficacy data. Among the 43 trials, 16 were phase I, 20 phase II, and 4 phase I/II. No phase III trials have been reported. While both novel and classic NCs have been explored in urologic cancers, NCs already approved for the treatment of other cancers were more widely represented. Trials in prostate cancer and mixed trials involving both urologic and non-urologic cancer patients were the most commonly reported trials. Although NCs have demonstrable efficacy with adequate safety in non-urologic cancer patient populations, current clinical stage NC options appear to be less beneficial in the urologic cancer setting. For example, nab-paclitaxel and liposomal doxorubicin have proven ineffective in the treatment of urologic cancers despite successes in other cancers. However, several ongoing pre-clinical studies using targeted and locally applied improved NCs may eventually improve their utility.
Topics: Male; Humans; Urologic Neoplasms; Prostatic Neoplasms
PubMed: 38161104
DOI: 10.1016/j.urolonc.2023.11.022 -
Nanomedicine : Nanotechnology, Biology,... Nov 2023There are four kinds of taxanes: solvent-based paclitaxel (Sb-P), liposomal paclitaxel (Lps-P), nanoparticle albumin-bound paclitaxel (Nab-P), and docetaxel. This study...
Efficacy comparisons of solvent-based paclitaxel, liposomal paclitaxel, nanoparticle albumin-bound paclitaxel, and docetaxel after neoadjuvant systemic treatment in breast cancer.
PURPOSE
There are four kinds of taxanes: solvent-based paclitaxel (Sb-P), liposomal paclitaxel (Lps-P), nanoparticle albumin-bound paclitaxel (Nab-P), and docetaxel. This study aims to retrospectively evaluate the efficacy of different taxanes on neoadjuvant systemic treatment (NST) in breast cancer.
METHODS
Patients who were diagnosed with breast cancer and had received integral NST from August 2013 to April 2022 were enrolled. The efficacy was divided into total pathological complete response (total-pCR), breast pathological complete response (breast-pCR), and axillary pathological complete response (axillary-pCR) for in-depth analysis and discussion.
RESULTS
The choice of taxane was an independent risk factor for total-pCR and breast-pCR rates. The highest total-pCR and breast-pCR rates were found in the Nab-P group. The difference was not significant among all the taxanes in the axillary-pCR rate.
CONCLUSION
Nab-P significantly improved the total-pCR and breast-pCR rates. It should be the first choice among taxanes in NST for breast cancer.
Topics: Humans; Female; Breast Neoplasms; Docetaxel; Albumin-Bound Paclitaxel; Neoadjuvant Therapy; Retrospective Studies; Paclitaxel; Albumins; Taxoids; Nanoparticles; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37717927
DOI: 10.1016/j.nano.2023.102707