Delivery of Gemcitabine Prodrugs Employing Mesoporous Silica Nanoparticles

Malfanti, Alessio; Miletto, Ivana; Bottinelli, Emanuela Diana; Zonari, Daniele; Blandino, Giulia; Berlier, Gloria

doi:10.3390/molecules21040522

Cited by 33 publications

(21 citation statements)

References 59 publications

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“…The change is in the order HA200A < HA6.4B @ HA200B. Both phenomena are usually observed in MCM-41-like materials after functionalization and/or drug encapsulation, and are interpreted in terms of molecules filling/lining the pores [50,51].…”

Section: Effect Of Conjugation On Porous Structurementioning

confidence: 81%

Hyaluronated mesoporous silica nanoparticles for active targeting: influence of conjugation method and hyaluronic acid molecular weight on the nanovector properties

Ricci

Zonari

Cannito

et al. 2018

Journal of Colloid and Interface Science

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We have prepared and evaluated the physico-chemical and biological properties of four different hyaluronated mesoporous silica nanoparticles (MSNs) samples (MSN/HA). Hyaluronic acid (HA) with two different molecular weights (200 and 6.4 kDa) was used for the conjugation of aminopropyl-functionalized MSN (NH-MSN), following two different procedures. Namely, samples HA200A and HA6.4A were prepared by reacting activated HA with NH-MSN (method A), while samples HA200B and HA6.4B were obtained carrying out HA activation in the presence of the nanoparticles (method B). The four samples showed similar hydrophilicity, but clear differences in the HA loading, textural properties, surface charge and stability of the suspensions. More in detail, conjugation using low molecular weight HA with method A resulted in low HA loading, with consequent scarce effects on dispersity and stability in physiological media. The highest yield and corresponding best performances were obtained with method B using high molecular weight HA. HA loading and molecular weight also influenced in a concerted way the biological response towards the MSNs of CD44 target cancer cells (CD44) and control cells (CD44): MDA-MB-231 and A2780, respectively. The absence of cytotoxicity was assessed. Moreover, the targeting ability of the best performing MSN/HA was confirmed by cellular uptake studies.

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Section: Effect Of Conjugation On Porous Structurementioning

confidence: 81%

Hyaluronated mesoporous silica nanoparticles for active targeting: influence of conjugation method and hyaluronic acid molecular weight on the nanovector properties

Ricci

Zonari

Cannito

et al. 2018

Journal of Colloid and Interface Science

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“…The zeta potential of MSN-NH 2 and MSN-FA was found to be positive, but MSN-Met has shown negative zeta potential. Another possible reason for this phenomena (lower loading of DTX into MSN-Met) could be due to the steric hindrance of the epiclon–Met on the surfaces of MSNs resulting in acting as a band for entrance of DTX 55,56. In addition, the in vitro release profiles of DTX from MSNs under different pH conditions were drawn as shown in Figure 6.…”

Section: Resultsmentioning

confidence: 99%

Mesoporous silica nanoparticles functionalized with folic acid/methionine for active targeted delivery of docetaxel

Khosravian¹,

Ardestani²,

Khoobi³

et al. 2016

OTT

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Mesoporous silica nanoparticles (MSNs) are known as carriers with high loading capacity and large functionalizable surface area for target-directed delivery. In this study, a series of docetaxel-loaded folic acid- or methionine-functionalized mesoporous silica nanoparticles (DTX/MSN-FA or DTX/MSN-Met) with large pores and amine groups at inner pore surface properties were prepared. The results showed that the MSNs were successfully synthesized, having good pay load and pH-sensitive drug release kinetics. The cellular investigation on MCF-7 cells showed better performance of cytotoxicity and cell apoptosis and an increase in cellular uptake of targeted nanoparticles. In vivo fluorescent imaging on healthy BALB/c mice proved that bare MSN-NH2 are mostly accumulated in the liver but MSN-FA or MSN-Met are more concentrated in the kidney. Importantly, ex vivo fluorescent images of tumor-induced BALB/c mice organs revealed the ability of MSN-FA to reach the tumor tissues. In conclusion, DTX/MSNs exhibited a good anticancer activity and enhanced the possibility of targeted drug delivery for breast cancer.

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“…It is reported that PDMS is particularly vulnerable to adsorption by hydrophobic molecules where adsorption becomes significant for molecules with partition coefficients greater than 2.47 [5]. Doxorubicin, having a partition coefficient of 1.27 [67], is relatively hydrophilic and is expected to be only minimally adsorbed within PDMS (>10%). There are no known studies on potential PDMS adsorption of DOX-HANP.…”

Section: Discussionmentioning

confidence: 99%

Differential response to doxorubicin in breast cancer subtypes simulated by a microfluidic tumor model

Özçelikkale

Shin

Noe-Kim

et al. 2017

Journal of Controlled Release

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Successful drug delivery and overcoming drug resistance are the primary clinical challenges for management and treatment of cancer. The ability to rapidly screen drugs and delivery systems within physiologically relevant environments is critically important; yet is currently limited due to lack of appropriate tumor models. To address this problem, we developed the Tumor-microenvironment-on-chip (T-MOC), a new microfluidic tumor model simulating the interstitial flow, plasma clearance, and transport of the drug within the tumor. We demonstrated T-MOC’s capabilities by assessing the delivery and efficacy of doxorubicin in small molecular form versus hyaluronic acid nanoparticle (NP) formulation in MCF-7 and MDA-MB-231, two cell lines representative of different molecular subtypes of breast cancer. Doxorubicin accumulated and penetrated similarly in both cell lines while the NP accumulated more in MDA-MB-231 than MCF-7 potentially due to binding of hyaluronic acid to CD44 expressed by MDA-MB-231. However, the penetration of the NP was less than the molecular drug due to its larger size. In addition, both cell lines cultured on the T-MOC showed increased resistance to the drug compared to 2D culture where MDA-MB-231 attained a drug-resistant tumor-initiating phenotype indicated by increased CD44 expression. When grown in immunocompromised mice, both cell lines exhibited cell-type-dependent resistance and phenotypic changes similar to T-MOC, confirming its predictive ability for in vivo drug response. This initial characterization of T-MOC indicates its transformative potential for in vitro testing of drug efficacy towards prediction of in vivo outcomes and investigation of drug resistance mechanisms for advancement of personalized medicine.

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Delivery of Gemcitabine Prodrugs Employing Mesoporous Silica Nanoparticles

Cited by 33 publications

References 59 publications

Hyaluronated mesoporous silica nanoparticles for active targeting: influence of conjugation method and hyaluronic acid molecular weight on the nanovector properties

Hyaluronated mesoporous silica nanoparticles for active targeting: influence of conjugation method and hyaluronic acid molecular weight on the nanovector properties

Mesoporous silica nanoparticles functionalized with folic acid/methionine for active targeted delivery of docetaxel

Differential response to doxorubicin in breast cancer subtypes simulated by a microfluidic tumor model

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