Peptide‐labeled supramolecular aggregates as selective doxorubicin carriers for delivery to tumor cells

Abstract

New liposomal aggregates, prepared by combining together, in a 90:10 molar ratio, two amphiphilic monomers, one containing two hydrocarbon chains in the hydrophobic region and the anionic DOTA chelating agent as hydrophilic moiety, and the other containing the same hydrophobic moiety and the CCK8 peptide, are described. The liposomal aggregates because of the presence of the specific moiety, constituted by the CCK8 peptide, which selectively recognizes CCK receptors on tumor cells are used as drug carriers with the aim to deliver into tumor cells the appropriate antitumor drug. The drug loading content and the releasing properties of the liposomal aggregates are studied by the use of the cytotoxic doxorubicin as drug model. The doxorubicin loading content determination reveals that above 95% of the total drug was uptaken with a corresponding drug/lipid w/w ratio of 0.134. The cellular uptake of the targeted liposomal doxorubicin with respect to the self-assembled, nonspecific, liposomal doxorubicin is evaluated using flow cytometry assays. The doxorubicin cell content for two types of cell systems, namely, A431 and HuVEC cells, for peptide derivatized liposomes was 70- and 8-fold higher, respectively, than for nontargeted liposomes, indicating that the bioactive CCK8 peptide is able to enhance the doxorubicin uptake into the carcinoma cells in vitro. The cytotoxicity effect of liposomal doxorubicin on A431 cells has been assessed by MTT assays: in presence of drug amounts ranged between 250 and 1000 ng/ml, incubation with peptide derivatized liposomes showed significantly lower cell survival compared with nontargeted liposomes.

Peptide-modified liposomes for selective targeting of bombesin receptors overexpressed by cancer cells: a potential theranostic agent

“…Moreover, the authors also studied liposomes prepared by co-aggregation of a synthetic amphiphilic monomer containing both the bioactive peptide and the chelating agent, with commercial phospholipids. In both cases, targeted nanocarriers engineered to conjugate imaging and therapeutic functions [20][21][22][23][24] were obtained for potential theranostic applications. Derivatized nanosystems, capable of diagnosis, drug delivery, and monitoring of therapeutic response, are expected to play a significant role in the dawning era of personalized medicine.…”

Peptide-based targeting strategies for simultaneous imaging and therapy with nanovectors

“…(C18) 2 DOTA/(C18) 2 L5CCK8 (90/10) liposomes showed comparable results. 59 Very recently, the same authors described new BN-conjugated nanosystems for theranostic purposes. 60 The liposomes are based on the co-aggregation of a DSPC phospholipid with MonY-BN, a new synthetic amphiphilic monomer ( Figure 2) containing a 7-14-Bombesin peptide fragment, DTPA chelating agent, hydrophobic moiety with two C18 alkyl chains, and PEG spacers.…”

Review peptide‐targeted liposomes for selective drug delivery: Advantages and problematic issues

“…Two liposomes decorated with CCK8 peptide and loaded with DOX have been developed for the targeting of the cholecystokinin subtype receptors A (or CCK1‐R) and B (or CCK2‐R) . CCK1‐R has been found to be overexpressed in gastroenteropancreatic neuroendocrine tumors, meningiomas and in certain neuroblastomas; whereas CCK2‐R has been found to be overexpressed in stromal ovarian cancers, medullary thyroid cancers, astrocytomas and small‐cell lung cancers .…”