Rapid transport of deformation-tuned nanoparticles across biological hydrogels and cellular barriers

Abstract

To optimally penetrate biological hydrogels such as mucus and the tumor interstitial matrix, nanoparticles (NPs) require physicochemical properties that would typically preclude cellular uptake, resulting in inefficient drug delivery. Here, we demonstrate that (poly(lactic-co-glycolic acid) (PLGA) core)-(lipid shell) NPs with moderate rigidity display enhanced diffusivity through mucus compared with some synthetic mucus penetration particles (MPPs), achieving a mucosal and tumor penetrating capability superior to that of both their soft and hard counterparts. Orally administered semi-elastic NPs efficiently overcome multiple intestinal barriers, and result in increased bioavailability of doxorubicin (Dox) (up to 8 fold) compared to Dox solution. Molecular dynamics simulations and super-resolution microscopy reveal that the semi-elastic NPs deform into ellipsoids, which enables rotation-facilitated penetration. In contrast, rigid NPs cannot deform, and overly soft NPs are impeded by interactions with the hydrogel network. Modifying particle rigidity may improve the efficacy of NP-based drugs, and can be applicable to other barriers.

Bioinspired Multivalent Peptide Nanotubes for Sialic Acid Targeting and Imaging‐Guided Treatment of Metastatic Melanoma

“…In contrast, I‐PPNTs deeply penetrated into the tumor tissue and diffused throughout the tumor sections, implying the superior tumor penetrating ability of PBA‐functionalized PNTs. This would be most likely explained by rotation‐facilitated deep tumor penetration of rod‐shaped nanoparticles as reported by Gao and coworkers . Noticeably, the red fluorescence of ICG and green fluorescence of GFP colocalized well in the I‐PPNT‐treated tumor sections, implying highly efficient internalization of the peptide nanotubes.…”

Membrane penetration and trapping of an active particle

“…Inserting the latter equation into Eq. (20) and setting the left-hand side to zero, the steady-state distance separating the self-driven particle from the central particles is given by…”

“…Considerable research advances have been made over the last few years in understanding the penetration of particles into cell membranes. Previous studies have shown that the particle uptake by living cells is strongly affected by the particle properties [20][21][22][23][24] and the physicochemical and functional properties of the membrane [25][26][27][28][29][30] .…”

Micro/Nano Motor Navigation and Localization via Deep Reinforcement Learning

“…The potential of such motors has been demonstrated in emerging applications like drug delivery, precision surgery, and environmental remediation. [ 1,3,4,10–16 ]…”