Abstract:Background
The aim of this work was to develop a novel and feasible modification strategy by utilizing the supramolecular effect of 2-hydroxypropyl-beta-cyclodextrin (2-HP-β-CD) for enhancing the biological transport efficiency of paclitaxel (PTX)-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles.
Methods
PTX-loaded 2-HP-β-CD-modified PLGA nanoparticles (2-HP-β-CD/PLGA NPs) were prepared using the modified emulsion method. Nano-characteristics, drug release behavio… Show more
“…Consequently, the drug circulation time is prolonged and drug accumulation at cancerous sites is enhanced. 22 , 32 Figure 6 Evaluation of the biological distribution of CD@R848@NPs in vivo: ( a ) In vivo tumor targeting and biodistribution of IR-780, IR-780-R848@NPs, and IR-780-CD@R848@NPs. IR-780 equivalent dose, 100 µg/kg.…”
Section: Resultsmentioning
confidence: 99%
“… 21 Moreover, 2-HP-β-CD has a natural affinity to macrophages. 22 This compound naturally gravitates toward macrophages and can effectively solubilize numerous drugs that are usually insoluble in water. Recently, researchers have investigated the ability of R848-loaded cyclodextrin nanoparticles to enhance TAM targeting in vivo.…”
Section: Introductionmentioning
confidence: 99%
“…The morphology and state of the nanoparticles were investigated using transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC) techniques. 22 Comprehensive in vitro and in vivo evaluations were conducted to determine the therapeutic potential of combining CD@R848@NPs with anti-TNFR2 (A-T) in a cancer model ( Figure 1b ). This approach might offer a straightforward and universally applicable strategy for delivering other hydrophobic cancer drugs on demand.…”
Purpose
This study aimed to develop a novel and feasible modification strategy to improve the solubility and antitumor activity of resiquimod (R848) by utilizing the supramolecular effect of 2-hydroxypropyl-beta-cyclodextrin (2-HP-β-CD).
Methods
R848-loaded PLGA nanoparticles modified with 2-HP-β-CD (CD@R848@NPs) were synthesized using an enhanced emulsification solvent-evaporation technique. The nanoparticles were then characterized in vitro by several methods, such as scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, particle size analysis, and zeta potential analysis. Then, the nanoparticles were loaded with IR-780 dye and imaged using an in vivo imaging device to evaluate their biodistribution. Additionally, the antitumor efficacy and underlying mechanism of CD@R848@NPs in combination with an anti-TNFR2 antibody were investigated using an MC-38 colon adenocarcinoma model in vivo.
Results
The average size of the CD@R848@NPs was 376 ± 30 nm, and the surface charge was 21 ± 1 mV. Through this design, the targeting ability of 2-HP-β-CD can be leveraged and R848 is delivered to tumor-supporting M2-like macrophages in an efficient and specific manner. Moreover, we used an anti-TNFR2 antibody to reduce the proportion of Tregs. Compared with plain PLGA nanoparticles or R848, CD@R848@NPs increased penetration in tumor tissues, dramatically reprogrammed M1-like macrophages, removed tumors and prolonged patient survival.
Conclusion
The new nanocapsule system is a promising strategy for targeting tumor, reprogramming tumor -associated macrophages, and enhancement immunotherapy.
“…Consequently, the drug circulation time is prolonged and drug accumulation at cancerous sites is enhanced. 22 , 32 Figure 6 Evaluation of the biological distribution of CD@R848@NPs in vivo: ( a ) In vivo tumor targeting and biodistribution of IR-780, IR-780-R848@NPs, and IR-780-CD@R848@NPs. IR-780 equivalent dose, 100 µg/kg.…”
Section: Resultsmentioning
confidence: 99%
“… 21 Moreover, 2-HP-β-CD has a natural affinity to macrophages. 22 This compound naturally gravitates toward macrophages and can effectively solubilize numerous drugs that are usually insoluble in water. Recently, researchers have investigated the ability of R848-loaded cyclodextrin nanoparticles to enhance TAM targeting in vivo.…”
Section: Introductionmentioning
confidence: 99%
“…The morphology and state of the nanoparticles were investigated using transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC) techniques. 22 Comprehensive in vitro and in vivo evaluations were conducted to determine the therapeutic potential of combining CD@R848@NPs with anti-TNFR2 (A-T) in a cancer model ( Figure 1b ). This approach might offer a straightforward and universally applicable strategy for delivering other hydrophobic cancer drugs on demand.…”
Purpose
This study aimed to develop a novel and feasible modification strategy to improve the solubility and antitumor activity of resiquimod (R848) by utilizing the supramolecular effect of 2-hydroxypropyl-beta-cyclodextrin (2-HP-β-CD).
Methods
R848-loaded PLGA nanoparticles modified with 2-HP-β-CD (CD@R848@NPs) were synthesized using an enhanced emulsification solvent-evaporation technique. The nanoparticles were then characterized in vitro by several methods, such as scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, particle size analysis, and zeta potential analysis. Then, the nanoparticles were loaded with IR-780 dye and imaged using an in vivo imaging device to evaluate their biodistribution. Additionally, the antitumor efficacy and underlying mechanism of CD@R848@NPs in combination with an anti-TNFR2 antibody were investigated using an MC-38 colon adenocarcinoma model in vivo.
Results
The average size of the CD@R848@NPs was 376 ± 30 nm, and the surface charge was 21 ± 1 mV. Through this design, the targeting ability of 2-HP-β-CD can be leveraged and R848 is delivered to tumor-supporting M2-like macrophages in an efficient and specific manner. Moreover, we used an anti-TNFR2 antibody to reduce the proportion of Tregs. Compared with plain PLGA nanoparticles or R848, CD@R848@NPs increased penetration in tumor tissues, dramatically reprogrammed M1-like macrophages, removed tumors and prolonged patient survival.
Conclusion
The new nanocapsule system is a promising strategy for targeting tumor, reprogramming tumor -associated macrophages, and enhancement immunotherapy.
“…Due to its formation of an inclusion complex with CD, PTX was employed. 150 The resulting hydrogels were characterized for their mechanical and rheological properties, in vitro anticancer effect on PC-3 PCa cells and drug release in vitro . The mechanical properties of the hydrogels were reduced upon the addition of β-CyD-moieties compared to the unmodified sample, but the kinetics of gelatin did not vary much.…”
Section: Recent Applications Of Ptx Nanomedicine For the Treatment Of...mentioning
Cancer has reached a wide dimension in the current era. There is a need to develop advanced therapeutic methods that can effectively inhibit the proliferation of precancer and malignant tumors....
“…3 However, due to the indiscriminate killing effect of chemotherapy i.e. killing cancer cells along with normal cells, 4 there are many side effects caused by chemotherapy, such as immune system damage, kidney failure, etc. 5 Therefore, the development of targeted chemotherapy strategies is necessary and promising.…”
Chemotherapy is one of the effective ways to treat cancer because of its ability to control lesions quickly. However, chemotherapy can have many side effects due to chemotherapy indiscriminately...
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