Polyanionic Biopolymers for the Delivery of Pt(II) Cationic Antiproliferative Complexes

Abstract

Phenanthriplatin, that is, (SP-4-3)-diamminechlorido(phenanthridine)platinum(II) nitrate, an effective antitumor cationic Pt(II) complex, was loaded on negatively charged dextran sulfate (DS) as a model vector for drug delivery via electrostatic interactions. The free complex and the corresponding conjugate with DS were tested on two standard human tumor cell lines, namely, ovarian A2780 and colon HCT 116, and on several malignant pleural mesothelioma cell lines (namely, epithelioid BR95, mixed/biphasic MG06, sarcomatoid MM98, and sarcomatoid cisplatin-resistant MM98R). The in vitro results suggest that the conjugate releases the active metabolite phenanthriplatin with a biphasic fashion. In these experimental conditions, the conjugate is slightly less active than free phenanthriplatin; but both exhibited antiproliferative potency higher than the reference metallodrug cisplatin and were able to overcome the acquired cisplatin chemoresistance in MM98R cells.

Pt(IV)/Re(I) Chitosan Conjugates as a Flexible Platform for the Transport of Therapeutic and/or Diagnostic Anticancer Agents

“…On the contrary, phenanthriplatin (i.e., (SP-4-3)-diamminechlorido(phenanthridine)platinum(II) nitrate) loaded on negatively charged dextran sulfate, a polysaccharide not very different from chitosan, resulted in slightly less active than free phenanthriplatin. Also, in this case, the slightly lower AR (3.03 for conjugate vs. 4.81 for free complex) may justify this behavior [42]. Chitosan proved not to be an efficient carrier for the studied metal drugs: it increases the AR of the free Pt complex but it does not reach high levels.…”

Malignant Pleural Mesothelioma: State of the art and advanced cell therapy

“…Free complex and conjugated with DS revealed higher antiproliferative activity in many tumour cell lines and could bypass acquired cisplatin resistance on MPM cells. [16]…”

How to obtain Pt(iv) complexes suitable for conjugation to nanovectors from the oxidation of [PtCl(terpyridine)]+

“…Thus, phenanthriplatin proved to be very effective on several cell lines. [9][10][11][12][13][14][15] Recently, triamine (or in general monofunctional) Pt(II) complexes have been re-evaluated as anticancer drugs, 16 since carefully designed ligands allow the resulting Pt compounds to bind with DNA in a different manner. This could result in alternative cell death mechanisms and/or circumvention of Pt resistance.…”