Engineering multi-stage nanovectors for controlled degradation and tunable release kinetics

Abstract

Nanovectors hold substantial promise in abating the off-target effects of therapeutics by providing a means to selectively accumulate payloads at the target lesion, resulting in an increase in the therapeutic index. A sophisticated understanding of the factors that govern the degradation and release dynamics of these nanovectors is imperative to achieve these ambitious goals. In this work, we elucidate the relationship that exists between variations in pore size and the impact on the degradation, loading, and release of multistage nanovectors. Larger pored vectors displayed faster degradation and higher loading of nanoparticles, while exhibiting the slowest release rate. The degradation of these particles was characterized to occur in a multi-step progression where they initially decreased in size leaving the porous core isolated, while the pores gradually increased in size. Empirical loading and release studies of nanoparticles along with diffusion modeling revealed that this prolonged release was modulated by the penetration within the porous core of the vectors regulated by their pore size.

Effects of pore size on in vitro and in vivo anticancer efficacies of mesoporous silica nanoparticles

“…MSN8 with large pore size might load DOX into deeper pore channel, thus leading to longer diffusion distance and slower release rate. 20 Although a large pore size could allow for easy accommodation of the guest molecular, it did not guarantee efficient release kinetics. 21,22 Therefore, MSN5 with the medium pore size would be an appropriate drug carrier in view of higher LC and more efficient in vitro release behavior.…”

Use of Ferritin-Based Metal-Encapsulated Nanocarriers as Anticancer Agents

“…Nanocarrier (NC) systems are suitable for several applications, including cell-specific or tissue-specific drug delivery, biomedical imaging and therapy [1,2]. Many types of materials are used for the synthesis of NC: among these, special attention is given to protein cage structures, such as ferritins (Fts), because they are self-assembling, highly symmetrical proteins, with a strictly controlled size.…”

Physicochemical Properties Affect the Synthesis, Controlled Delivery, Degradation and Pharmacokinetics of Inorganic Nanoporous Materials

“…The pore sizes of pSi materials can range from 2 to 100 nm and further pore enlargement could be achieved using both thermal and chemical methods [29]. Furthermore, by adjusting the porosity of pSi one can modulate the biodegradation [30] inducing tailorable degradation and release profiles and photonic properties to generate distinct 'barcodes' that can be detected using simple fluorescent methods [22]. The two main pore morphologies fabricated in pSi materials generally comprise two types of cylindrical pores: interconnected/branched and dead ended [31].…”