Clinical outcomes of conventional drug combinations are not ideal due to high toxicity to healthy tissues. Cisplatin (CDDP) is the standard component for many cancer treatments, yet its principal dose-limiting side effect is nephrotoxicity. Thus, CDDP is commonly used in combination with other drugs, such as the autophagy inhibitor chloroquine (CQ), to enhance tumor cell killing efficacy and prevent the development of chemoresistance. In addition, nanocarrier-based drug delivery systems can overcome chemotherapy limitations, decreasing side effects and increasing tumor accumulation. The aim of this study was to evaluate the toxicity of CQ and CDDP against tumor and non-tumor cells when used in a combined treatment. For this purpose, two types of micelles based on Pluronic® F127 hybrid dendritic–linear–dendritic block copolymers (HDLDBCs) modified with polyester or poly(esteramide) dendrons derived from 2,2′-bis(hydroxymethyl)propionic acid (HDLDBC-bMPA) or 2,2′-bis(glycyloxymethyl)propionic acid (HDLDBC-bGMPA) were explored as delivery nanocarriers. Our results indicated that the combined treatment with HDLDBC-bMPA(CQ) or HDLDBC-bGMPA(CQ) and CDDP increased cytotoxicity in tumor cells compared to the single treatment with CDDP. Encapsulations demonstrated less short-term cytotoxicity individually or when used in combination compared to the free drugs. However, and more importantly, a low degree of cytotoxicity against non-tumor cells was maintained, even when drugs were given simultaneously.
(1) Background: Biophysical techniques applied to serum samples characterization could promote the development of new diagnostic tools. Fluorescence spectroscopy has been previously applied to biological samples from cancer patients and differences from healthy individuals were observed. Dendronized hyperbranched polymers (DHP) based on bis(hydroxymethyl)propionic acid (bis-MPA) were developed in our group and their potential biomedical applications explored. (2) Methods: A total of 94 serum samples from diagnosed cancer patients and healthy individuals were studied (20 pancreatic ductal adenocarcinoma, 25 blood donor, 24 ovarian cancer, and 25 benign ovarian cyst samples). (3) Results: Fluorescence spectra of serum samples (fluorescence liquid biopsy, FLB) in the presence and the absence of DHP-bMPA were recorded and two parameters from the signal curves obtained. A secondary parameter, the fluorescence spectrum score (FSscore), was calculated, and the diagnostic model assessed. For pancreatic ductal adenocarcinoma (PDAC) and ovarian cancer, the classification performance was improved when including DHP-bMPA, achieving high values of statistical sensitivity and specificity (over 85% for both pathologies). (4) Conclusions: We have applied FLB as a quick, simple, and minimally invasive promising technique in cancer diagnosis. The classification performance of the diagnostic method was further improved by using DHP-bMPA, which interacted differentially with serum samples from healthy and diseased subjects. These preliminary results set the basis for a larger study and move FLB closer to its clinical application, providing useful information for the oncologist during patient diagnosis.
Evaluation of PEG-b-polycarbonates self-assemblies containing azobenzene or coumarin moieties as nanocarriers using paclitaxel as a model hydrophobic drugAim: The work assesses the performance of nanocarriers from amphiphilic block copolymers with functional azobenzene or coumarin moieties for delivery of paclitaxel.Methods: Placlitaxel was encapsulated by the nanoprecipitation method.Characterizations were performed by DLS, TEM, Zeta potential and HPLC. Cell viability was investigated in HeLa and Huh-5-2-cell lines.Results: Coumarin-containing polymeric micelles (Dh = 26±2 nm, PDI = 0.28, ζ = -22.9±3.6 mV) with 11.2±0.5 %w/w drug loading showed enhanced cytotoxicity in HeLa cells (IC50 < 0.02 nM) compared to free paclitaxel (IC50 = 0.17±0.02 nM). Azobenzene-containing polymeric vesicles (Dh = 390±20 nm, PDI = 0.24, ζ = -33.2±5.0 mV) with a 6.8±0.4 %w/w drug loading showed increased cytotoxicity under 530 nm light (IC50 = 0.0114±0.00033 nM) in HeLa cells due to a stimulated delivery of paclitaxel. Conclusion:Effectivity of these block copolymers as paclitaxel nanovectors and light stimulated release has been demonstrated.
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