Conjugation to Poly(amidoamine) Dendrimers and Pulmonary Delivery Reduce Cardiac Accumulation and Enhance Antitumor Activity of Doxorubicin in Lung Metastasis

Zhong, Qian; Bielski, Elizabeth; Rodrigues, Leonan S.; Brown, Matthew; Reineke, Joshua; Rocha, Sandro R. P. da

doi:10.1021/acs.molpharmaceut.6b00126

Cited by 76 publications

(36 citation statements)

References 76 publications

(155 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In treating of lung metastasis mouse model, as indicated by increased survival rates and decreased tumor burden, DOX conjugated to carboxyl-terminated poly(amidoamine) dendrimers (PAMAM) was more effective than DOX delivered intravenously [50].…”

Section: Dendrimers [15-145 Nm]mentioning

confidence: 99%

Synergistic Effects of Nanomedicine Targeting TNFR2 and DNA Demethylation Inhibitor—An Opportunity for Cancer Treatment

Al-Hatamleh

Boer

et al. 2019

Cells

View full text Add to dashboard Cite

Tumor necrosis factor receptor 2 (TNFR2) is expressed on some tumor cells, such as myeloma, Hodgkin lymphoma, colon cancer and ovarian cancer, as well as immunosuppressive cells. There is increasingly evidence that TNFR2 expression in cancer microenvironment has significant implications in cancer progression, metastasis and immune evasion. Although nanomedicine has been extensively studied as a carrier of cancer immunotherapeutic agents, no study to date has investigated TNFR2-targeting nanomedicine in cancer treatment. From an epigenetic perspective, previous studies indicate that DNA demethylation might be responsible for high expressions of TNFR2 in cancer models. This perspective review discusses a novel therapeutic strategy based on nanomedicine that has the capacity to target TNFR2 along with inhibition of DNA demethylation. This approach may maximize the anti-cancer potential of nanomedicine-based immunotherapy and, consequently, markedly improve the outcomes of the management of patients with malignancy.Cells 2020, 9, 33 2 of 16 and tumor cells [6][7][8]. In contrast, TNFR2 expression was only reported on tumor cells and suppressive immune cells, suggesting that TNFR2 directly promotes cancer development [9]. Furthermore, the latest preclinical and clinical studies confirmed the implication of TNF-TNFR2 signaling in cancer proliferation and the suppression of immune response [10,11]. Consequently, blockade of TNF-TNFR2 axis could be a promising option for cancer treatment (Figure 1).On the other hand, nanotechnology provided several platforms in the field of immunotherapy and made significant advances towards safe and efficient targeting systems with positive clinical outcomes and minimal side effects; this is the so-called field of nanomedicine [12]. Despite the emerging trends of using nanoparticles in immunotherapy, no studies have investigated any type of nanocarriers to target TNFR2 on cancer cells. However, based on some previous novel reports about the effects of nanoparticles on immune homeostasis [13], especially using nanoparticles to promote TNFR2 + Foxp3 + regulatory T cells (Tregs) in inflammatory models [14,15], we have suggested in our recent perspective review the possibility of blocking TNF-TNFR2 axis via nanoparticles [16].

show abstract

Section: Dendrimers [15-145 Nm]mentioning

confidence: 99%

Synergistic Effects of Nanomedicine Targeting TNFR2 and DNA Demethylation Inhibitor—An Opportunity for Cancer Treatment

Al-Hatamleh

Boer

et al. 2019

Cells

View full text Add to dashboard Cite

show abstract

“…Subsequent studies have also examined the pulmonary pharmacokinetics of PAMAM dendrimers in rodents [49][50][51]. For instance, Zhong et al compared the pulmonary and intravenous pharmacokinetics of G3 amine-terminated and PEGylated PAMAM dendrimers in mice [51].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…In addition, the doxorubicin solution formulation induced significant pulmonary toxicity after a single dose, whereas the doxorubicin conjugate was well tolerated after twice weekly dosing over 2 weeks. Similarly, PAMAM dendrimers have also been examined for their ability to improve the treatment of lung-resident cancers after pulmonary administration of a doxorubicinconjugated G4 PAMAM dendrimer [50]. This complex showed pH-dependent drug release with maximal drug liberation (80%) at an acidic pH (pH 4.5).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Polymer-drug conjugates as inhalable drug delivery systems: A review

Marasini

Haque

Kaminskas

2017

Current Opinion in Colloid & Interface Science

View full text Add to dashboard Cite

Abstract:Accelerating interest by the pharmaceutical industry in the identification and development of less invasive routes of nanomedicine administration, coupled with defined efforts to improve the treatment of respiratory diseases through inhaled drug administration has fuelled growing interests in inhalable polymer-drug conjugates. Polymer-drug conjugates can alter the pharmacokinetics profile of the loaded drug after inhaled administration and enable the controlled and sustained exposure of the lungs to drugs when compared to the inhaled or oral administration of the drug alone. However, the major concern with the use of inhalable polymer-drug conjugates is their biocompatibility and long-term safety with the lungs, which is closely linked to their retention time in the lungs. A detailed understanding about the pharmacokinetics, lung disposition, clearance and safety of inhaled polymer-drug conjugates with significant translational potential is therefore required. This review therefore provides a comprehensive summary of the latest developments on several types of polymer-drug conjugates that are currently being explored as inhalable drug delivery systems. Finally, the current status and future perspective of the polymer-drug conjugates is also discussed with a focus on current knowledge gaps. Graphical abstract:

show abstract

“…Encapsulation of chemotherapeutics in nanocarriers, such as liposomes [6,7], nanoparticles [8,9], dendrimers [10,11] or micelles [12,13], which exploit the enhanced permeability and retention (EPR) effect, is the most extensively explored strategy for improving tumor bioavailability and reducing exposure to healthy tissues. However, these systems have had limited success, and only a small fraction (less than 1%) of the injected dose accumulates within the tumor, even in highly permeable tumors [14].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cells As Guideposts for Nanoparticle-Mediated Targeted Drug Delivery in Ovarian Cancer

Layek

Shetty

Nethi

et al. 2020

Cancers

View full text Add to dashboard Cite

Nanocarriers have been extensively utilized for the systemic targeting of various solid tumors and their metastases. However, current drug delivery systems, in general, suffer from a lack of selectivity for tumor cells. Here, we develop a novel two-step targeting strategy that relies on the selective accumulation of targetable synthetic receptors (i.e., azide moieties) in tumor tissues, followed by delivery of drug-loaded nanoparticles having a high binding affinity for these receptors. Mesenchymal stem cells (MSCs) were used as vehicles for the tumor-specific accumulation of azide moieties, while dibenzyl cyclooctyne (DBCO) was used as the targeting ligand. Biodistribution and antitumor efficacy studies were performed in both orthotopic metastatic and patient-derived xenograft (PDX) tumor models of ovarian cancer. Our studies show that nanoparticles are retained in tumors at a significantly higher concentration in mice that received azide-labeled MSCs (MSC-Az). Furthermore, we observed significantly reduced tumor growth (p < 0.05) and improved survival in mice receiving MSC-Az along with paclitaxel-loaded DBCO-functionalized nanoparticles compared to controls. These studies demonstrate the feasibility of a two-step targeting strategy for efficient delivery of concentrated chemotherapy for treating solid tumors.

show abstract

Conjugation to Poly(amidoamine) Dendrimers and Pulmonary Delivery Reduce Cardiac Accumulation and Enhance Antitumor Activity of Doxorubicin in Lung Metastasis

Cited by 76 publications

References 76 publications

Synergistic Effects of Nanomedicine Targeting TNFR2 and DNA Demethylation Inhibitor—An Opportunity for Cancer Treatment

Synergistic Effects of Nanomedicine Targeting TNFR2 and DNA Demethylation Inhibitor—An Opportunity for Cancer Treatment

Polymer-drug conjugates as inhalable drug delivery systems: A review

Mesenchymal Stem Cells As Guideposts for Nanoparticle-Mediated Targeted Drug Delivery in Ovarian Cancer

Contact Info

Product

Resources

About