Catalase-loaded cisplatin-prodrug-constructed liposomes to overcome tumor hypoxia for enhanced chemo-radiotherapy of cancer.
TL;DR: An exquisite type of liposome-based nanoparticles is developed in this work by integrating cisplatin-based chemotherapy and catalase-induced tumor hypoxia relief together for combined chemo-radiotherapy with great synergistic efficacy, promising for clinical translation in cancer treatment.
About: This article is published in Biomaterials.The article was published on 2017-09-01. It has received 191 citations till now. The article focuses on the topics: Tumor hypoxia & Cisplatin.
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TL;DR: Liposomes, an early version of LNPs, are a versatile nanomedicine delivery platform for treatment of a variety of diseases, such as antitumor and nucleic acid therapeutics and vaccine delivery systems as mentioned in this paper.
Abstract: Lipid nanoparticles (LNPs) have emerged across the pharmaceutical industry as promising vehicles to deliver a variety of therapeutics. Currently in the spotlight as vital components of the COVID-19 mRNA vaccines, LNPs play a key role in effectively protecting and transporting mRNA to cells. Liposomes, an early version of LNPs, are a versatile nanomedicine delivery platform. A number of liposomal drugs have been approved and applied to medical practice. Subsequent generations of lipid nanocarriers, such as solid lipid nanoparticles, nanostructured lipid carriers, and cationic lipid-nucleic acid complexes, exhibit more complex architectures and enhanced physical stabilities. With their ability to encapsulate and deliver therapeutics to specific locations within the body and to release their contents at a desired time, LNPs provide a valuable platform for treatment of a variety of diseases. Here, we present a landscape of LNP-related scientific publications, including patents and journal articles, based on analysis of the CAS Content Collection, the largest human-curated collection of published scientific knowledge. Rising trends are identified, such as nanostructured lipid carriers and solid lipid nanoparticles becoming the preferred platforms for numerous formulations. Recent advancements in LNP formulations as drug delivery platforms, such as antitumor and nucleic acid therapeutics and vaccine delivery systems, are discussed. Challenges and growth opportunities are also evaluated in other areas, such as medical imaging, cosmetics, nutrition, and agrochemicals. This report is intended to serve as a useful resource for those interested in LNP nanotechnologies, their applications, and the global research effort for their development.
394 citations
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Soochow University (Suzhou)1, Chinese Academy of Sciences2, Center for Excellence in Education3, University of Science and Technology of China4, Wuhan University5, Zhejiang University6, National Institutes of Health7, Hunan University8, Nanjing University9, Xiamen University10, Tsinghua University11, Huazhong University of Science and Technology12, University of Florida13
TL;DR: The recent advances of intelligent cancer nanomedicine are demonstrated, and the comprehensive understanding of their structure-function relationship for smart and efficient cancer nanotechine including various imaging and therapeutic applications, as well as nanotoxicity is discussed.
Abstract: Precise nanomedicine has been extensively explored for efficient cancer imaging and targeted cancer therapy, as evidenced by a few breakthroughs in their preclinical and clinical explorations. Here, we demonstrate the recent advances of intelligent cancer nanomedicine, and discuss the comprehensive understanding of their structure-function relationship for smart and efficient cancer nanomedicine including various imaging and therapeutic applications, as well as nanotoxicity. In particular, a few emerging strategies that have advanced cancer nanomedicine are also highlighted as the emerging focus such as tumor imprisonment, supramolecular chemotherapy, and DNA nanorobot. The challenge and outlook of some scientific and engineering issues are also discussed in future development. We wish to highlight these new progress of precise nanomedicine with the ultimate goal to inspire more successful explorations of intelligent nanoparticles for future clinical translations.
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TL;DR: Catalase-encapsulated hyaluronic-acid-based nanoparticles loaded with adamantane-modified photosensitizer for enhanced PDT of solid tumors showed high colloidal stability and monodispersity in aqueous solution and demonstrated a great potential in overcoming hypoxia for targeted PDT.
Abstract: Photodynamic therapy (PDT) as a treatment method has many advantages such as minimal invasiveness, repeatable dosage, and low systemic toxicity. Issues with conventional PDT agents include the limited availability of endogenous oxygen and difficulty in accumulation at the tumor site, which has hindered the successful treatment of tumors. Herein, we developed catalase-encapsulated hyaluronic-acid-based nanoparticles loaded with adamantane-modified photosensitizer for enhanced PDT of solid tumors. Chlorin e6 (Ce6) as the photosensitizer was modified with adamantane to yield adamantane-modified Ce6 (aCe6). The obtained nanosystem (HA-CAT@aCe6) could target overly expressed CD44 receptors on cancer cells, supplying oxygen by converting endogenous hydrogen peroxide (H2O2) to oxygen, and improving PDT efficacy upon light irradiation. HA-CAT@aCe6 nanoparticles showed high colloidal stability and monodispersity in aqueous solution. The uptake and targeting property of HA-CAT@aCe6 were demonstrated by confocal mic...
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TL;DR: In this review, the latest efforts utilizing nanomedicine to modulate various features within the microenvironment of solid tumors, including tumor hypoxia, tumor pH, the extracellular matrix, as well as the immune microenvironment within the tumor are summarized.
223 citations
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TL;DR: A new multimodal theranostic nanoconstruct based on Fe-doped polydiaminopyridine nanofusiforms, built easily and on a large scale, which can dual-regulate intracellular oxygen and glutathione levels, transport iron ions, and simultaneously be used for thermal imaging and magnetic resonance imaging is reported.
Abstract: Integration of multiple therapeutic/diagnostic modalities into a single system holds great promise to improve theranostic efficiency for tumors, but still remains a technical challenge. Herein, we report a new multimodal theranostic nanoconstruct based on Fe-doped polydiaminopyridine nanofusiforms, built easily and on a large scale, which can dual-regulate intracellular oxygen and glutathione levels, transport iron ions, and simultaneously be used for thermal imaging and magnetic resonance imaging. Co-loading of dihydroartemisinin and methylene blue generates a superior multifunctional theranostic agent with enhanced photochemotherapy efficiency and biodegradability, leading to almost complete destruction of tumors with near-infrared light irradiation. This represents an attractive route to develop multimodal anticancer theranostics.
208 citations
References
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TL;DR: Novel engineering approaches are discussed that capitalize on the growing understanding of tumour biology and nano–bio interactions to develop more effective nanotherapeutics for cancer patients.
Abstract: The intrinsic limits of conventional cancer therapies prompted the development and application of various nanotechnologies for more effective and safer cancer treatment, herein referred to as cancer nanomedicine. Considerable technological success has been achieved in this field, but the main obstacles to nanomedicine becoming a new paradigm in cancer therapy stem from the complexities and heterogeneity of tumour biology, an incomplete understanding of nano-bio interactions and the challenges regarding chemistry, manufacturing and controls required for clinical translation and commercialization. This Review highlights the progress, challenges and opportunities in cancer nanomedicine and discusses novel engineering approaches that capitalize on our growing understanding of tumour biology and nano-bio interactions to develop more effective nanotherapeutics for cancer patients.
3,800 citations
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TL;DR: Low-risk patients had estimates of 5-year PSA outcome after treatment with RP, RT, or implant with or without neoadjuvant androgen deprivation that were not statistically different, whereas intermediate- and high- risk patients treated with RP or RT did better then those treated by implant.
Abstract: Context.—Interstitial radiation (implant) therapy is used to treat clinically
localized adenocarcinoma of the prostate, but how it compares with other treatments
is not known.Objective.—To estimate control of prostate-specific antigen (PSA) after radical
prostatectomy (RP), external beam radiation (RT), or implant with or without
neoadjuvant androgen deprivation therapy in patients with clinically localized
prostate cancer.Design.—Retrospective cohort study of outcome data compared using Cox regression
multivariable analyses.Setting and Patients.—A total of 1872 men treated between January 1989 and October 1997 with
an RP (n=888) or implant with or without neoadjuvant androgen deprivation
therapy (n=218) at the Hospital of the University of Pennsylvania, Philadelphia,
or RT (n=766) at the Joint Center for Radiation Therapy, Boston, Mass, were
enrolled.Main Outcome Measure.—Actuarial freedom from PSA failure (defined as PSA outcome).Results.—The relative risk (RR) of PSA failure in low-risk patients (stage T1c,
T2a and PSA level ≤10 ng/mL and Gleason score ≤6) treated using RT,
implant plus androgen deprivation therapy, or implant therapy was 1.1 (95%
confidence interval [CI], 0.5-2.7), 0.5 (95% CI, 0.1-1.9), and 1.1 (95% CI,
0.3-3.6), respectively, compared with those patients treated with RP. The
RRs of PSA failure in the intermediate-risk patients (stage T2b or Gleason
score of 7 or PSA level >10 and ≤20 ng/mL) and high-risk patients (stage
T2c or PSA level >20 ng/mL or Gleason score ≥8) treated with implant compared
with RP were 3.1 (95% CI, 1.5-6.1) and 3.0 (95% CI, 1.8-5.0), respectively.
The addition of androgen deprivation to implant therapy did not improve PSA
outcome in high-risk patients but resulted in a PSA outcome that was not statistically
different compared with the results obtained using RP or RT in intermediate-risk
patients. These results were unchanged when patients were stratified using
the traditional rankings of biopsy Gleason scores of 2 through 4 vs 5 through
6 vs 7 vs 8 through 10.Conclusions.—Low-risk patients had estimates of 5-year PSA outcome after treatment
with RP, RT, or implant with or without neoadjuvant androgen deprivation that
were not statistically different, whereas intermediate- and high-risk patients
treated with RP or RT did better then those treated by implant. Prospective
randomized trials are needed to verify these findings.
3,408 citations
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TL;DR: This investigation investigated the effect of surgery plus postoperative (adjuvant) chemoradiotherapy on the survival of patients with resectable adenocarcinoma of the stomach or gastroesophageal junction.
Abstract: Background Surgical resection of adenocarcinoma of the stomach is curative in less than 40 percent of cases. We investigated the effect of surgery plus postoperative (adjuvant) chemoradiotherapy on the survival of patients with resectable adenocarcinoma of the stomach or gastroesophageal junction. Methods A total of 556 patients with resected adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to surgery plus postoperative chemoradiotherapy or surgery alone. The adjuvant treatment consisted of 425 mg of fluorouracil per square meter of body-surface area per day, plus 20 mg of leucovorin per square meter per day, for five days, followed by 4500 cGy of radiation at 180 cGy per day, given five days per week for five weeks, with modified doses of fluorouracil and leucovorin on the first four and the last three days of radiotherapy. One month after the completion of radiotherapy, two five-day cycles of fluorouracil (425 mg per square meter per day) plus leucovorin (20 mg per squar...
3,032 citations
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TL;DR: In patients with laryngeal cancer, radiotherapy with concurrent administration of cisplatin is superior to induction chemotherapy followed by radiotherapy or radiotherapy alone for larynGEal preservation and locoregional control.
Abstract: Background Induction chemotherapy with cisplatin plus fluorouracil followed by radiotherapy is the standard alternative to total laryngectomy for patients with locally advanced laryngeal cancer. The value of adding chemotherapy to radiotherapy and the optimal timing of chemotherapy are unknown. Methods We randomly assigned patients with locally advanced cancer of the larynx to one of three treatments: induction cisplatin plus fluorouracil followed by radiotherapy, radiotherapy with concurrent administration of cisplatin, or radiotherapy alone. The primary end point was preservation of the larynx. Results A total of 547 patients were randomly assigned to one of the three study groups. The median follow-up period was 3.8 years. At two years, the proportion of patients who had an intact larynx after radiotherapy with concurrent cisplatin (88 percent) differed significantly from the proportions in the groups given induction chemotherapy followed by radiotherapy (75 percent, P=0.005) or radiotherapy alone (70 ...
2,730 citations
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TL;DR: Adjuvant chemotherapy has a significant survival benefit in patients with resected pancreatic cancer, whereas adjuvant chemoradiotherapy has a deleterious effect on survival.
Abstract: background The effect of adjuvant treatment on survival in pancreatic cancer is unclear. We report the final results of the European Study Group for Pancreatic Cancer 1 Trial and update the interim results. methods In a multicenter trial using a two-by-two factorial design, we randomly assigned 73 patients with resected pancreatic ductal adenocarcinoma to treatment with chemoradiotherapy alone (20 Gy over a two-week period plus fluorouracil), 75 patients to chemotherapy alone (fluorouracil), 72 patients to both chemoradiotherapy and chemotherapy, and 69 patients to observation. results The analysis was based on 237 deaths among the 289 patients (82 percent) and a median follow-up of 47 months (interquartile range, 33 to 62). The estimated five-year survival rate was 10 percent among patients assigned to receive chemoradiotherapy and 20 percent among patients who did not receive chemoradiotherapy (P=0.05). The five-year survival rate was 21 percent among patients who received chemotherapy and 8 percent among patients who did not receive chemotherapy (P=0.009). The benefit of chemotherapy persisted after adjustment for major prognostic factors. conclusions Adjuvant chemotherapy has a significant survival benefit in patients with resected pancreatic cancer, whereas adjuvant chemoradiotherapy has a deleterious effect on survival.
2,436 citations