Cancer-derived exosomes loaded with ultrathin palladium nanosheets for targeted bioorthogonal catalysis

Abstract

The transformational impact of bioorthogonal chemistries has inspired new strategies for the in vivo synthesis of bioactive agents through non-natural means. Among these, palladium (Pd) catalysts have played a prominent role in the growing subfield of bioorthogonal catalysis by producing xenobiotics and uncaging biomolecules in living systems. However, delivering catalysts selectively to specific cell types still lags behind catalyst development. Here we have developed a bio-artificial device consisting of cancer-derived exosomes loaded with Pd catalysts by a method that enables the controlled assembly of Pd nanosheets directly inside the vesicles. This hybrid system mediates Pd-triggered dealkylation reactions in vitro and inside cells and displays preferential tropism for their progenitor cells. The use of Trojan exosomes to deliver abiotic Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Use of exosomes as vectors to carry advanced therapies

“…To solve this concern while achieving high encapsulations yields, some authors proposed the employment of passive methods in order to internalize an ionic precursor of the NPs followed by the in situ synthesis of the nanostructures directly inside the vesicles. 101 Still early times for clinical trials but as the research in this eld is growing very quickly, new information on preclinical studies would help to enhance the knowledge to be transfer to the clinic and to the market fairly soon.…”

“…95 Adipose stem cell, primary neuronal cells or macrophages have been also incubated with iron nanoparticles (USPIOs or SPIONS) and then EVs loaded within them were puried in order to generate microvesicles for MRI imaging and photodynamic therapy in vivo. [96][97][98] Although some authors suggest that the indirect labeling of source cells is not recommended for exosome loading, [99][100][101] it is one of the most widely employed techniques to achieve the encapsulation of NPs within exosomes (together with electroporation strategies).…”

“…This new hybrid system mediated Pd-triggered dealkylation reactions inside cells and displays a preferential tropism and selectivity for their parental cells. 101 Finally, instead of encapsulating nanoparticles into exosomes some studies reported the attachment of them by binding the NPs to the exosomal surface or by engineering the membrane of the vesicles to create new exosome-based nanoplatforms. As an example, Qi et al, created a dual-functional exosomes-based cluster by anchoring transferrin-conjugated SPIONs on exosome surface through interactions with the Tf-Tf receptor for cancer therapy.…”

Palladium-based nanomaterials for cancer imaging and therapy

“…The Pd devices could activate the release of SN-38 at desired locations and give rise to the production of 5-FU after intratumoral implanting (Figure 11 B) 116 . In addition, encapsulation of ultrathin Pd NSs in cancer cell derived vesicles (Pd-Exo) as new artificial biological devices was developed to achieve the selective delivery of Pd catalysts 113 . Pd-Exo could be uptaken with high efficiency to achieve the specific release of the anticancer drug panobinostat, thereby leading to a new strategy for realizing precisely targeted chemotherapy.…”

Bioorthogonal release of anticancer drugs via gold-triggered 2-alkynylbenzamide cyclization

“…In an emerging eld of study, researchers have extensively investigated metal-based uncaging of drugs/uorophores applicable in cell-or animal-based models. 3 Mainly employing metals like palladium and ruthenium, a number of examples have leaned heavily on some iteration of amine/alcohol release through masking groups that include azide, [4][5][6][7] allene, 8 allyl, 9,10 propargyl, [11][12][13][14][15][16][17][18][19][20][21][22] propargyloxycarbonyl (Proc), [19][20][21][22][23][24][25][26][27][28][29] and allyloxycarbonyl (Alloc). [10][11][12][28][29][30][31][32][33][34][35][36][37][38][39][40] Looking at current literature, a few areas of need can be clearly identied.…”