Preparation and evaluation of peptide-dendrimer-paclitaxel conjugates for treatment of heterogeneous stage 1 nonsmall cell lung cancer in 293T and L132 cell lines

Zhang, Weiwei; Wang, Yanchun; Kan, Xiang-ming; Wang, Xuemei; Geng, Dongmei

doi:10.4314/tjpr.v16i4.1

Cited by 15 publications

(2 citation statements)

References 14 publications

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“…PAMAM dendrimers are a class of synthetic star-burst polymers that possess well-defined structures as well as desirable properties such as non-toxicity, non-immunogenicity, and excellent water solubility. Their active terminal functional groups allow for chemical modification and bioconjugation to various bioactive molecules, enabling their use in diverse medical applications including cancer targeting and treatment, 35,36 drug delivery, 21,37 gene delivery, 38,39 photodynamic therapy, 40,41 sensors, 42,43 and imaging. 44,45 Furthermore, PAMAM dendrimers have been recognized for their ability to enhance water solubility of hydrophobic drug molecules.…”

Section: Resultsmentioning

confidence: 99%

Polyamidoamine dendrimer-mediated hydrogel for solubility enhancement and anti-cancer drug delivery

Bi,

Watts,

Dorman

et al. 2023

J Biomater Appl

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The application of hydrogels for anti-cancer drug delivery has garnered considerable interest in the medical field. Current cancer treatment approaches, such as chemotherapy and radiation therapy, often induce severe side effects, causing significant distress and substantial health complications to patients. Hydrogels present an appealing solution as they can be precisely injected into specific sites within the body, facilitating the sustainable release of encapsulated drugs. This localized treatment approach holds great potential for reducing toxicity levels and improving drug delivery efficacy. In this study we developed a hydrogel delivery system containing polyamidoamine (PAMAM) dendrimer and polyethylene glycol (PEG) for solubility enhancement and sustained delivery of hydrophobic anti-cancer drugs. The three selected model drugs, e.g. silibinin, camptothecin, and methotrexate, possess limited aqueous solubility and thus face restricted application. In the presence of vinyl sulfone functionalized PAMAM dendrimer at 45 mg/mL concentration, drug solubility is increased by 37-fold, 4-fold, and 10-fold for silibinin, camptothecin, and methotrexate, respectively. By further crosslinking of the functionalized PAMAM dendrimer and thiolated PEG, we successfully developed a fast-crosslinking hydrogel capable of encapsulating a significant payload of solubilized cancer drugs for sustained release. In water, the drug encapsulated hydrogels release 30%–80% of their loads in 1–4 days. MTT assays of J82 and MCF7 cells with various doses of drug encapsulated hydrogels reveal that cytotoxicity is observed for all three drugs on both J82 and MCF7 cell lines after 48 h. Notably, camptothecin exhibits higher cytotoxicity to both cell lines than silibinin and methotrexate, achieving up to 95% cell death at experimental conditions, despite its lower solubility. Our experiments provide evidence that the PAMAM dendrimer-mediated hydrogel system significantly improves the solubility of hydrophobic drugs and facilitates their sustained release. These findings position the system as a promising platform for controlled delivery of hydrophobic drugs for intratumoral cancer treatment.

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Section: Resultsmentioning

confidence: 99%

Polyamidoamine dendrimer-mediated hydrogel for solubility enhancement and anti-cancer drug delivery

Bi,

Watts,

Dorman

et al. 2023

J Biomater Appl

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show abstract

“…Polyamidoamine (PAMAM) dendrimers are described as carriers for anticancer drugs and can be easily modified at the terminal groups by to improve their specific targeting to tumor cells [10]. Paclitaxel (PTX) is one of the best anticancer drugs and is active against a wide spectrum of cancers.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of 177Lu-DOTA-DN(PTX)-BN for Selective and Concomitant Radio and Drug—Therapeutic Effect on Breast Cancer Cells

et al. 2019

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The peptide-receptor radionuclide therapy (PRRT) is a successful approach for selectively delivering radiation within tumor sites through specific recognition of radiolabeled peptides by overexpressed receptors on cancer cell surfaces. The efficacy of PRRT could be improved by using polymeric radio- and drug- therapy nanoparticles for a concomitant therapeutic effect on malignant cells. This research aimed to prepare and evaluate, a novel drug and radiation delivery nanosystem based on the 177Lu-labeled polyamidoamine (PAMAM) dendrimer (DN) loaded with paclitaxel (PTX) and functionalized on the surface with the Lys1Lys3(DOTA)-bombesin (BN) peptide for specific targeting to gastrin-releasing peptide receptors (GRPr) overexpressed on breast cancer cells. DN was first conjugated covalently to BN and DOTA (chemical moiety for lutetium-177 complexing) and subsequently loaded with PTX. The characterization by microscopic and spectroscopic techniques, in-vitro drug delivery tests as well as in in-vitro and in-vivo cellular uptake of 177Lu-DOTA-DN(PTX)-BN by T47D breast cancer cells (GRPr-positive), indicated the formation of an improved delivery nanosystem with target-specific recognition by GRPr. Results of the 177Lu-DOTA-DN(PTX)-BN effect on T47D cell viability (1.3%, compared with 10.9% of 177Lu-DOTA-DN-BN and 14.0% of DOTA-DN-(PTX)-BN) demonstrated the concomitant radiotherapeutic and chemotherapeutic properties of the polymeric nanosystem as a potential agent for the treatment of GRPr-positive tumors.

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A Comprehensive Review of Current Perspectives on Novel Drug Delivery Systems and Approaches for Lung Cancer Management

et al. 2021

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Preparation and evaluation of peptide-dendrimer-paclitaxel conjugates for treatment of heterogeneous stage 1 nonsmall cell lung cancer in 293T and L132 cell lines

Cited by 15 publications

References 14 publications

Polyamidoamine dendrimer-mediated hydrogel for solubility enhancement and anti-cancer drug delivery

Polyamidoamine dendrimer-mediated hydrogel for solubility enhancement and anti-cancer drug delivery

Synthesis and Evaluation of 177Lu-DOTA-DN(PTX)-BN for Selective and Concomitant Radio and Drug—Therapeutic Effect on Breast Cancer Cells

A Comprehensive Review of Current Perspectives on Novel Drug Delivery Systems and Approaches for Lung Cancer Management

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