A novel ‘smart’ PNIPAM-based copolymer for breast cancer targeted therapy: Synthesis, and characterization of dual pH/temperature-responsive lactoferrin-targeted PNIPAM-co-AA

Metawea, Osama R. M.; Abdelmoneem, Mona A.; Haiba, Nesreen S.; Khalil, Hosam H.; Teleb, Mohamed; Elzoghby, Ahmed O.; Khafaga, Asmaa F.; Noreldin, Ahmed E.; Alberício, Fernando; Khattab, Sherine N.

doi:10.1016/j.colsurfb.2021.111694

Cited by 49 publications

(32 citation statements)

References 73 publications

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“…Additionally, the natural state of HK exists in a crystalline form and reveals its melting peak at approximately 72.43°C. The DSC thermogram of HK-loaded PMT-ALG/LF-RST NHs F9 showed only an endothermic peak at 341.29°C, con rming the loading of HK within NHs in an amorphous form [40].…”

Section: Development Of Crosslinked Hk-loaded Pmt-alg/lf-rst Nhsmentioning

confidence: 85%

Sequential Delivery of a Novel Triple Drug Combination via Crosslinked Alginate/lactoferrin Nanohybrids for Enhanced Breast Cancer Treatment

Salah

Sallam

Abdelmoneem

et al. 2022

Preprint

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While breast cancer remains a global health concern, the elaboration of rationally designed drug combinations coupled with advanced biocompatible delivery systems offers new promising treatment venues. Herein, we repurposed rosuvastatin (RST) based on its selective tumor apoptotic effect and combined it with the antimetabolite pemetrexed (PMT) and the tumor-sensitizing polyphenol honokiol (HK). This synergistic three-drug combination was incorporated into protein polysaccharide nanohybrids fabricated utilizing sodium alginate (ALG) and lactoferrin (LF), inspired by the stealth property of the former and the cancer cell targeting capability of the latter. ALG was conjugated to PMT and then coupled with LF conjugated to RST, forming core shell nanohybrids into which HK was physically loaded followed by cross linking using genipin. The crosslinked HK-loaded PMT-ALG/LF-RST nanohybrids exhibited fair drug loading of 7.86, 5.24 and 6.11% for RST, PMT and HK, respectively. It demonstrated an 8-fold decrease in the IC50 compared to the free drug combination, in addition to showing enhanced cellular uptake by MCF-7 cells. The in vivo antitumor efficacy in a breast cancer-bearing mouse model confirmed the superiority of the triple cocktail-loaded nanohybrids, as demonstrated by suppression of tumor growth and inhibition of ki-67 and VEGF-1 expression in addition to upregulation of caspase-3 expression. Conclusively, our rationally designed triple drug-loaded protein/polysaccharide nanohybrids offer a promising, biocompatible approach for effective breast tumor suppression.

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Section: Development Of Crosslinked Hk-loaded Pmt-alg/lf-rst Nhsmentioning

confidence: 85%

Sequential Delivery of a Novel Triple Drug Combination via Crosslinked Alginate/lactoferrin Nanohybrids for Enhanced Breast Cancer Treatment

Salah

Sallam

Abdelmoneem

et al. 2022

Preprint

Self Cite

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“…Breast cancer is the most common carcinoma and a leading cause of cancer mortality in women, with ∼2,000,000 new cases and 626,000 fatalities globally every year (1,2). So far, great progress has been made on the treatments for breast cancer, such as surgical resection, neoadjuvant therapy, adjuvant therapy, endocrinotherapy, and targeted therapy (3)(4)(5)(6)(7). Among these treatments, resection is a predominant strategy.…”

Section: Introductionmentioning

confidence: 99%

Incidence and Related Factors for Low-Extremity Deep Vein Thrombosis in Breast Cancer Patients Who Underwent Surgical Resection: What Do We Know and What Should We Care

et al. 2022

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Malignancy, surgical resection, and neoadjuvant and/or adjuvant chemotherapy increase the low-extremity deep vein thrombosis (LDVT) risk in patients with breast cancer, bringing in great physical burdens, disabilities, and worse survivals. However, LDVT in surgical breast cancer patients is scarcely reported. Therefore, this study aimed to evaluate the incidence and related factors for LDVT in these patients. Patients with breast cancer who underwent surgical resection were included. LDVT was examined on the day of discharge and 1 month after the discharge. A total of 491 eligible patients were included, among which 11 (2.2%) patients occurred LDVT. Besides, higher age, history of diabetes mellitus, advanced T and tumor node metastasis (TNM) stages, higher platelet count, and shorter activated partial thromboplastin time (APTT) were correlated with increased LDVT incidence (all p < 0.05). Additionally, higher age [p = 0.004, odds ratio (OR) (95% CI): 1.082 (1.023–1.144)], history of diabetes mellitus [p = 0.003, OR (95% CI): 10.426 (2.219–48.986)], and a higher platelet count [p = 0.008, OR (95% CI): 1.017 (1.004–1.029)] were independent factors for increased LDVT incidence, while higher APTT [p = 0.004, OR (95% CI): 0.636 (0.467–0.866)] was an independent factor for decreased LDVT incidence. Lastly, the risk prediction model involving age, history of diabetes mellitus, platelet count, and APTT showed a good ability to predict LDVT occurrence (area under curve: 0.919, 95% CI: 0.869–0.968). In conclusion, the LDVT incidence is 2.2%, and its independent factors consist of age, history of diabetes mellitus, platelet count, and APTT in patients with breast cancer who underwent surgical resection, which provides evidence for the prevention and surveillance of LDVT in surgical breast cancer.

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“…Sensitive DDS can undergo physical or chemical phase transformations in response to environmental factor stimuli, such as temperature, pH, enzymes, and light ( Ahmadi et al, 2020 ; Alvarez-Lorenzo et al, 2020 ; Ghaffar et al, 2020 ). For example, poly(N-isopropylacrylamide) (PNIPAM) is a typical sensitive polymer material because of its unique temperature sensitivity (its lower critical solution temperature (LCST) comes approximately 32°C) ( Metawea et al, 2021 ). When the temperature is above the LCST, PNIPAM will undergo a sharp phase transition from a coiled hydrophilic conformation to a collapsed hydrophobic conformation ( Liu et al, 2020 ; Yadav et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Upper-Critical-Solution-Temperature Polymer Modified Gold Nanorods for Laser Controlled Drug Release and Enhanced Anti-Tumour Therapy

Que

Jia

et al. 2021

Front. Pharmacol.

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Photothermal therapy (PTT) has become effective method for the treatment of malignant cancer. The development of PTT system with high anti-tumour effect is still the feasible research direction. Here, a new type of gold nanorods (AuNRs)-doxorubicin (DOX)/mPEG10K-peptide/P(AAm-co-AN) (APP-DOX) nano drug delivery system was proposed. Among them, AuNRs was used as high-efficiency photothermal agent. APP-DOX had a suitable size and can be targeted to accumulate in tumour tissues through circulation in the body. The abundant matrix metalloproteinase 2 (MMP-2) in the tumour environment intercepted and cut off the short peptide chain structure grafted on APP-DOX. At the same time, the removal of the PEG segment leaded to an increase in the hydrophobic properties of the system. Nanoparticles aggregated into large particles, causing them to stay and aggregate further at the tumour site. When irradiated by 808 nm near-infrared laser, APP-DOX achieved a gradual heating process. High temperature can effectively ablate tumours and enable UCST polymer to achieve phase transition, resulting in more anti-cancer drugs loaded in the polymer layer DOX was released, effectively killing cancer cells. Animal experiments had verified the possibility of the nano drug-carrying system and good tumour treatment effect. What’s more worth mentioning is that compared with free DOX, the nano drug delivery system had lower biological toxicity and not cause obvious harmful effects on normal organs and tissues.

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A novel ‘smart’ PNIPAM-based copolymer for breast cancer targeted therapy: Synthesis, and characterization of dual pH/temperature-responsive lactoferrin-targeted PNIPAM-co-AA

Cited by 49 publications

References 73 publications

Sequential Delivery of a Novel Triple Drug Combination via Crosslinked Alginate/lactoferrin Nanohybrids for Enhanced Breast Cancer Treatment

Sequential Delivery of a Novel Triple Drug Combination via Crosslinked Alginate/lactoferrin Nanohybrids for Enhanced Breast Cancer Treatment

Incidence and Related Factors for Low-Extremity Deep Vein Thrombosis in Breast Cancer Patients Who Underwent Surgical Resection: What Do We Know and What Should We Care

Upper-Critical-Solution-Temperature Polymer Modified Gold Nanorods for Laser Controlled Drug Release and Enhanced Anti-Tumour Therapy

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