Plasmonic photothermal release of docetaxel by gold nanoparticles incorporated onto halloysite nanotubes with conjugated 2D8-E3 antibodies for selective cancer therapy

Abstract

Background Applied nanomaterials in targeted drug delivery have received increased attention due to tangible advantages, including enhanced cell adhesion and internalization, controlled targeted release, convenient detection in the body, enhanced biodegradation, etc. Furthermore, conjugation of the biologically active ingredients with the drug-containing nanocarriers (nanobioconjugates) has realized impressive opportunities in targeted therapy. Among diverse nanostructures, halloysite nanotubes (NHTs) with a rolled multilayer structure offer great possibilities for drug encapsulation and controlled release. The presence of a strong hydrogen bond network between the rolled HNT layers enables the controlled release of the encapsulated drug molecules through the modulation of hydrogen bonding either in acidic conditions or at higher temperatures. The latter can be conveniently achieved through the photothermal effect via the incorporation of plasmonic nanoparticles. Results The developed nanotherapeutic integrated natural halloysite nanotubes (HNTs) as a carrier; gold nanoparticles (AuNPs) for selective release; docetaxel (DTX) as a cytotoxic anticancer agent; human IgG1 sortilin 2D8-E3 monoclonal antibody (SORT) for selective targeting; and 3-chloropropyltrimethoxysilane as a linker for antibody attachment that also enhances the hydrophobicity of DTX@HNT/Au-SORT and minimizes DTX leaching in body’s internal environment. HNTs efficiently store DTX at room temperature and release it at higher temperatures via disruption of interlayer hydrogen bonding. The role of the physical expansion and disruption of the interlayer hydrogen bonding in HNTs for the controlled DTX release has been studied by dynamic light scattering (DLS), electron microscopy (EM), and differential scanning calorimetry (DSC) at different pH conditions. HNT interlayer bond disruption has been confirmed to take place at a much lower temperature (44 °C) at low pH vs. 88 °C, at neutral pH thus enabling the effective drug release by DTX@HNT/Au-SORT through plasmonic photothermal therapy (PPTT) by light interaction with localized plasmon resonance (LSPR) of AuNPs incorporated into the HNT pores. Conclusions Selective ovarian tumor targeting was accomplished, demonstrating practical efficiency of the designed nanocomposite therapeutic, DTX@HNT/Au-SORT. The antitumor activity of DTX@HNT/Au-SORT (apoptosis of 90 ± 0.3%) was confirmed by in vitro experiments using a caov-4 (ATCC HTB76) cell line (sortilin expression > 70%) that was successfully targeted by the sortilin 2D8-E3 mAb, tagged on the DTX@HNT/Au. Graphic abstract

Enhanced antimicrobial treatment by a clay-based drug nanocarrier conjugated to a guanidine-rich cell penetrating peptide

“…In the acidic conditions, this H-bond network is dissociated and consequently the loaded drug is released. 51 This structural feature of the HNTs results in the huge prevention of drug leaching in the pH-neutral environments. The release amount of VCM and OFX were monitored by UV-vis absorbance spectroscopy, via the same procedure explained in the section of drug content estimation.…”

“…Finally, the obtained powder was dried in the vacuum oven and stored in a sterilized glass flask, under N 2 gas. 51 …”

Nanoscale bioconjugates: A review of the structural attributes of drug-loaded nanocarrier conjugates for selective cancer therapy

“…), silicone, layered double hydroxides, nanoporous materials, MXenes, and many others are some instances of synthesized nanomaterials [ 3 , 4 ]. According to the convenient synthesis approaches, high specific surface area, exciting physicochemical properties, easy functionalization and conjugation, nanomaterials have been applied as catalysts [ 5 , 6 , 7 , 8 ], magnetically separable catalysts [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ], photocatalyst [ 25 , 26 ], solar cells [ 27 , 28 ], supercapacitors [ 29 , 30 ], drug carriers [ 31 , 32 , 33 ], tissue engineering [ 34 ], biological facets [ 35 ], water treatment [ 36 , 37 ], etc., with high efficiencies.…”

Convenient synthesis of dipeptide structures in solution phase assisted by a thioaza functionalized magnetic nanocatalyst

“…The external shells can isolate the magnetic cores and protect them in the high-temperature processes. Silica, which is commonly employed as a support material in core–shell structures, not only enhances the stability of the nanoparticles (NPs) in a certain condition, but also allows them to be readily modified with various functional groups 24 , 25 .…”