Anticancer Drug Delivery: An Update on Clinically Applied Nanotherapeutics

Marchal, Sophie; Hor, Amélie El; Millard, Marie; Gillon, Véronique; Bezdetnaya, Lina

doi:10.1007/s40265-015-0453-3

Cited by 92 publications

(65 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…93 PEGylated liposomal formulations of DOX (Doxil ® /Caelyx ® ) were already applied in patients with satisfying results in terms of reduced cardiotoxicity, albeit no significant enhancement of therapeutic efficacy has been achieved. 4 The limited tumor distribution of DOX, which was shown to be restricted to the vascular region in vivo and to the outer rim in spheroids, is detrimental to its cytotoxic potential and fully justifies the investigations aiming to increase DOX efficiency, especially by the enhancement of both DOX accumulation and distribution in cancer tissues. 53,67 This issue is particularly crucial in the context of multidrug …”

Section: Drug Efficacy Depends On Np Behavior In Mctsmentioning

confidence: 99%

“…Nanotherapeutics issued from promising preclinical studies often failed to achieve the expected results in patients, and as such, nanomedicine is still considered challenging for cancer therapy. 4 To be efficiently delivered to the tumor, nanoparticles (NPs) must overcome different biological barriers that influence the extent of tissue penetration. Molecule diffusion through the interstitial space strongly depends on the structure and composition of the interstitial compartment.…”

Section: Introductionmentioning

confidence: 99%

“…Abraxane, a PTX albumin-based natural polymer, has been approved for clinical use, and other nanoformulations continue to be developed, some of them being evaluated in ongoing clinical trials. 4,99 Docetaxel (DTX), another taxane used as an anticancer drug, is in theory fourfold more potent than PTX but …”

mentioning

confidence: 99%

“…The PS meta-tetra(hydroxyphenyl) chlorine (mTHPC; Foscan ® ) is a potent PS approved for the treatment of head and neck carcinoma, but its poor pharmacokinetics properties leading to skin photosensitivity considerably limited its clinical application. 4 Liposomal formulations of mTHPC (Foslip ® , Fospeg ® ) provided some improvements with regard to pharmacokinetics in tumor-bearing mice, but the capacity of the mTHPC-loaded liposomes to penetrate the tumor tissue remained unknown until recently. 4,102 The high fluorescence quantum yield of mTHPC allows the accurate tracing of PS penetration into the MCTS.…”

mentioning

confidence: 99%

“…4 Liposomal formulations of mTHPC (Foslip ® , Fospeg ® ) provided some improvements with regard to pharmacokinetics in tumor-bearing mice, but the capacity of the mTHPC-loaded liposomes to penetrate the tumor tissue remained unknown until recently. 4,102 The high fluorescence quantum yield of mTHPC allows the accurate tracing of PS penetration into the MCTS. 32,103 It was shown that irrespective of formulation (free mTHPC, Foslip ® or Fospeg ® ), the PS fluorescence was limited to the outer rim of the spheroid with a slightly higher drug content for liposomal mTHPC formulations.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening

Millard¹,

Yakavets²,

Zorin³

et al. 2017

IJN

Self Cite

105

107

View full text Add to dashboard Cite

The increasing number of publications on the subject shows that nanomedicine is an attractive field for investigations aiming to considerably improve anticancer chemotherapy. Based on selective tumor targeting while sparing healthy tissue, carrier-mediated drug delivery has been expected to provide significant benefits to patients. However, despite reduced systemic toxicity, most nanodrugs approved for clinical use have been less effective than previously anticipated. The gap between experimental results and clinical outcomes demonstrates the necessity to perform comprehensive drug screening by using powerful preclinical models. In this context, in vitro three-dimensional models can provide key information on drug behavior inside the tumor tissue. The multicellular tumor spheroid (MCTS) model closely mimics a small avascular tumor with the presence of proliferative cells surrounding quiescent cells and a necrotic core. Oxygen, pH and nutrient gradients are similar to those of solid tumor. Furthermore, extracellular matrix (ECM) components and stromal cells can be embedded in the most sophisticated spheroid design. All these elements together with the physicochemical properties of nanoparticles (NPs) play a key role in drug transport, and therefore, the MCTS model is appropriate to assess the ability of NP to penetrate the tumor tissue. This review presents recent developments in MCTS models for a better comprehension of the interactions between NPs and tumor components that affect tumor drug delivery. MCTS is particularly suitable for the high-throughput screening of new nanodrugs.

show abstract

Section: Drug Efficacy Depends On Np Behavior In Mctsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening

Millard¹,

Yakavets²,

Zorin³

et al. 2017

IJN

Self Cite

105

107

View full text Add to dashboard Cite

show abstract

Self‐Assembling Doxorubicin Prodrug Forming Nanoparticles and Effectively Reversing Drug Resistance In Vitro and In Vivo

Mao

Huang

et al. 2016

Adv Healthcare Materials

View full text Add to dashboard Cite

Doxorubicin (DOX) is a widely used chemotherapeutic drug to treat a range of cancers. However, its unfavorable effects, particularly the cardiotoxicity and the induction of multidrug resistance (MDR), significantly limit its clinical applications. Herein, a novel doxorubicin prodrug, PEG -DOX, is synthesized by conjugating a deprotonated doxorubicin molecule with the polyethylene glycol (PEG, MW: 2K) chain via pH-responsive hydrazone bond, and its potential as a better alternative than doxorubicin is evaluated. The data show that the amphiphilic PEG -DOX can self-assemble into stable nanoparticles with a high and fixed doxorubicin loading content (≈20 wt%), a favorable size of 91.5 nm with a narrow polydispersity (PDI = 0.14), good stability, and pH-dependent release behavior due to the acid-cleavable linkage between PEG and doxorubicin. Although doxorubicin hardly accumulates in MDR cells, PEG -DOX nanoparticles significantly increase the cellular uptake and cell-killing activity of doxorubicin in two MDR cancer cell lines MCF-7/ADR and KBv200, with the IC values dropped to 1.130% and 42.467% of doxorubicin, respectively. More impressively, PEG -DOX nanoparticles exhibit significantly improved plasma pharmacokinetics, increased in vivo therapeutic efficacy against MDR xenograft tumors, and better in vivo safety compared with doxorubicin. PEG -DOX nanoparticles hold the promise to become a better alternative than doxorubicin for cancer treatment, especially for MDR tumors.

show abstract

Hypoxia‐Induced Pro‐Protein Therapy Assisted by a Self‐Catalyzed Nanozymogen

Wei

et al. 2020

Angewandte Chemie

View full text Add to dashboard Cite

The success of intracellular protein therapy demands efficient delivery and selective protein activity in diseased cells. Therefore, a cascaded nanozymogen consisting of a hypoxia‐activatable pro‐protein, a hypoxia‐inducing protein, and a hypoxia‐strengthened intracellular protein delivery nanovehicle was developed. RPAB, an enzymatically inactive pro‐protein of RNase, reversibly caged with hypoxia‐cleavable azobenzene, was delivered with glucose oxidase (GOx) using hypoxia‐responsive nanocomplexes (NCs) consisting of azobenzene‐cross‐linked oligoethylenimine (AOEI) and hyaluronic acid (HA). Upon NC‐mediated delivery into cancer cells, GOx catalyzed glucose decomposition and aggravated tumoral hypoxia, which drove the recovery of RPAB back to the hydrolytically active RNase and expedited the degradation of AOEI to release more protein cargoes. Thus, the catalytic reaction of the nanozymogen was self‐accelerated and self‐cycled, ultimately leading to a cooperative anti‐cancer effect between GOx‐mediated starvation therapy and RNase‐mediated pro‐apoptotic therapy.

show abstract

Anticancer Drug Delivery: An Update on Clinically Applied Nanotherapeutics

Cited by 92 publications

References 68 publications

Drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening

Drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening

Self‐Assembling Doxorubicin Prodrug Forming Nanoparticles and Effectively Reversing Drug Resistance In Vitro and In Vivo

Hypoxia‐Induced Pro‐Protein Therapy Assisted by a Self‐Catalyzed Nanozymogen

Contact Info

Product

Resources

About