Strategies to improve tumor penetration of nanomedicines through nanoparticle design

Zhang, Ya‐Ru; Lin, Run; Li, Hong‐Jun; He, Weiling; Du, Jin‐Zhi; Wang, Jun

doi:10.1002/wnan.1519

Cited by 194 publications

(153 citation statements)

References 68 publications

Supporting

Mentioning

150

Contrasting

Order By: Relevance

“…In addition, an exhaustive understanding of the factors that guide the tissue penetration is extremely urgent. Size, shape, and surface chemistry have been identified as the major characteristics responsible for NCs diffusion inside the tumor mass [44,45]. Beside some universally accepted correlation, such as the inverse proportion between NC size and penetration ability, there are still controversial opinions about the impact of surface charge [46,47].…”

Section: Tumor-specific Accumulationmentioning

confidence: 99%

Thirty Years of Cancer Nanomedicine: Success, Frustration, and Hope

Salvioni

Rizzuto

Bertolini

et al. 2019

Cancers

141

135

View full text Add to dashboard Cite

Starting with the enhanced permeability and retention (EPR) effect discovery, nanomedicine has gained a crucial role in cancer treatment. The advances in the field have led to the approval of nanodrugs with improved safety profile and still inspire the ongoing investigations. However, several restrictions, such as high manufacturing costs, technical challenges, and effectiveness below expectations, raised skeptical opinions within the scientific community about the clinical relevance of nanomedicine. In this review, we aim to give an overall vision of the current hurdles encountered by nanotherapeutics along with their design, development, and translation, and we offer a prospective view on possible strategies to overcome such limitations.

show abstract

Section: Tumor-specific Accumulationmentioning

confidence: 99%

Thirty Years of Cancer Nanomedicine: Success, Frustration, and Hope

Salvioni

Rizzuto

Bertolini

et al. 2019

Cancers

141

135

View full text Add to dashboard Cite

show abstract

“…This increases the outward interstitial flow and thereby limits convective transport into the tumour region [9]. Nanoparticle transport to the centre of the tumour is thus impeded and nanoparticles hardly reach the tumour core or any regions located further away from functioning vasculature as shown in Fig 6B. As summed up by Zhang et al [63], the elevated IF pressure is one of the main factors that hinders effective tumour penetration of nanoparticles. Goel et al [64] state that vascular normalisation reduces tumour hypoxia as well as the IF pressure.…”

Section: Discussionmentioning

confidence: 91%

Extension of a multiphase tumour growth model to study nanoparticle delivery to solid tumours

et al. 2020

View full text Add to dashboard Cite

One of the main challenges in increasing the efficacy of conventional chemotherapeutics is the fact that they do not reach cancerous cells at a sufficiently high dosage. In order to remedy this deficiency, nanoparticle-based drugs have evolved as a promising novel approach to more specific tumour targeting. Nevertheless, several biophysical phenomena prevent the sufficient penetration of nanoparticles in order to target the entire tumour. We therefore extend our vascular multiphase tumour growth model, enabling it to investigate the influence of different biophysical factors on the distribution of nanoparticles in the tumour microenvironment. The novel model permits the examination of the interplay between the size of vessel-wall pores, the permeability of the blood-vessel endothelium and the lymphatic drainage on the delivery of particles of different sizes. Solid tumours develop a non-perfused core and increased interstitial pressure. Our model confirms that those two typical features of solid tumours limit nanoparticle delivery. Only in case of small nanoparticles is the transport dominated by diffusion, and particles can reach the entire tumour. The size of the vessel-wall pores and the permeability of the blood-vessel endothelium have a major impact on the amount of delivered nanoparticles. This extended in-silico tumour growth model permits the examination of the characteristics and of the limitations of nanoparticle delivery to solid tumours, which currently complicate the translation of nanoparticle therapy to a clinical stage. OPEN ACCESSCitation: Wirthl B, Kremheller J, Schrefler BA, Wall WA (2020) Extension of a multiphase tumour growth model to study nanoparticle delivery to solid tumours. PLoS ONE 15(2): e0228443. https://

show abstract

“…Furthermore this effective formulation will likely enhance drug delivery to tumor sites, and overcome current issues in delivering HDACi to solid tumors, whilst also reducing side effects associated with systemic delivery of the free drug. The enhanced permeability and retention effect (EPR) would enable these nanoparticles to escape via neo-vascularization at tumor sites, and subsequently their physico-chemical characteristics would allow better penetration into solid tumors [63][64][65][66]. Such parameters are likely to be speci c to different cancer types, even when just considering Pluronic, where differences in e cacy can be observed [67,68].…”

Section: Discussionmentioning

confidence: 99%

Nanomicelles Potentiate HDAC Inhibitor Efficacy In Vitro.

Pisano

Wang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background. Amphiphilic block copolymers used as nanomicelle drug carriers can effectively overcome poor drug solubility and specificity issues. Hence, these platforms have a broad applicability in cancer treatment. In this study, Pluronic F127 was used to fabricate nanomicelles containing the histone deacetylase inhibitor SAHA, which has an epigenetic-driven anti-cancer effect in several tumor types. SAHA loaded nanomicelles were prepared using a thin-film drying method and characterized for size, surface charge, drug content and drug release properties. Loaded particles were tested for in vitro activity and their effect on cell-cycle and markers of metastasis. Results. Following detailed particle characterization, cell proliferation experiments demonstrated that SAHA loaded nanomicelles more effectively inhibited the growth of HeLa and MCF-7 cell lines compared with free drug formulations. The 30nm SAHA containing nanoparticles were able to release up to 100% of the encapsulated drug over a 72h time window. Moreover, gene and protein expression analyses suggested that this effect was achieved through the regulation of p21 and p53 expression. SAHA was also shown to upregulate E-cadherin expression, potentially influencing tumor migration and metastasis.Conclusions. This study highlights the opportunity to exploit pluronic-based nanomicelles for the delivery of compounds that regulate epigenetic processes, thus inhibiting cancer development and progression.

show abstract

Strategies to improve tumor penetration of nanomedicines through nanoparticle design

Cited by 194 publications

References 68 publications

Thirty Years of Cancer Nanomedicine: Success, Frustration, and Hope

Thirty Years of Cancer Nanomedicine: Success, Frustration, and Hope

Extension of a multiphase tumour growth model to study nanoparticle delivery to solid tumours

Nanomicelles Potentiate HDAC Inhibitor Efficacy In Vitro.

Contact Info

Product

Resources

About