Photodynamic therapy (PDT) is a relatively noninvasive therapeutic method for treating several pathologies. PDT involves the use of light and a photosensitizer (PS) to generate reactive oxygen species (ROS), which cause injury and, finally, cellular death [1]. PDT has been used for cancer therapy and cosmetic purposes [2]. The Food and Drug Administration (FDA) has approved PDT as a treatment for several conditions. These include skin diseases like advanced cutaneous T-cell lymphoma and basal cell carcinoma, gastrointestinal disorders such as Barrett's esophagus and esophageal cancer, and some lung diseases, including lung cancer [3]. Antimicrobial photodynamic therapy (aPDT) uses the PDT principle but is applied to microorganisms and is considered a promising approach for preventing and treating local infections [4]. The main benefits of aPDT include its effectiveness against a broad range of pathogens, especially resistant strains, and its inability to cause resistance even after repeated exposure. The local application of PSs in the infected area, combined with targeted light treatment, reduces side effects compared to systemic therapies [[5], [6], [7], [8]]. Furthermore, microorganisms bind and internalize the PS much more rapidly than the adjacent host cells [9].

The rise of multidrug-resistant bacteria has become a problem in public health. Among these, the “ESKAPE” bacteria are pathogens known for resisting almost all antibiotics. This group includes Enterococcus faecium, Staphylococcus aureus (S. aureus), Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa (P. aeruginosa), and Enterobacter species [10]. Thus, aPDT is a promising strategy to inactivate these resistant bacteria. In general, Gram-negative bacteria are less susceptible to antibiotics than Gram-positive bacteria. This intrinsic feature is attributed to cell wall differences that limit drug entrance into bacterial cells. It is important to remark that this resistance is independent of other mechanisms. Gram-negative bacteria are characterized by an outer lipopolysaccharide membrane, which surrounds the thinner peptidoglycan layer. In contrast, Gram-positive bacteria have a thick and porous peptidoglycan layer. Consequently, in aPDT, Gram-positive bacteria are more easily photoinactivated than Gram-negative bacteria [11,12]. Lipopolysaccharides on the outer membrane of Gram-negative bacteria confer them a negative charge on the surface; therefore, neutral or negatively charged PSs are not effectively incorporated. A strategy could be applying cationic PSs to favor the interaction with bacteria and enhance the antibacterial effect [13].

Over time, three generations of PSs have been developed for aPDT [14]. The latest generation (third) overcame the limitations of the previous versions, including the incorporation into nanocarriers. In line with this, phthalocyanines (Pcs) are second generation PSs with absorption in the near-infrared (NIR) region, elevated extinction molar coefficient, and high efficiency in ROS generation (including singlet oxygen 1O2) [15]. As a limitation, the majority of Pcs are lipophilic, which compromises their behavior in aqueous environments. Therefore, incorporation of Pcs into drug delivery systems can improve this drawback. Several carriers have been used to transport Pcs in aPDT, including polymeric materials such as micelles, nanoparticles, films, gold, silver, silica nanoparticles, liposomes (Lips), and quantum dots, among others [[15], [16], [17], [18]].

Nanocarriers play a significant role in PDT [19]. In aPDT, similar effects have been observed, including improved solubility, stability, and bioavailability of PSs, as well as facilitating their delivery to target sites, and enhancing cellular uptake. These systems also protect PSs from premature degradation and promote their selective accumulation at infection sites, ultimately leading to improved therapeutic outcomes [[20], [21], [22], [23], [24]]. Lips are vesicles composed of phospholipid bilayers surrounding an aqueous compartment. Both hydrophilic and hydrophobic drugs can be loaded into Lips [25]. Hydrophobic PSs can be accommodated in the hydrophobic chains of phospholipids. The phospholipid type and the cholesterol addition modulate liposome properties as rigidity or surface charge. The incorporation of positively charged lipids makes cationic liposomes (CLips) [12]. Although incorporating PSs into CLips is promising, only a few works studied their performance in aPDT [14]. In this work, a Zn(II) phthalocyanine (ZnPc) was incorporated into zwitterionic and CLips to evaluate their performance in S. aureus, Escherichia coli (E. coli) and P. aeruginosa all of which belong to the ESKAPE group. S. aureus is a Gram-positive bacterium associated with infections in soft tissues and surgical cuts or wounds. Also, in some immunosuppressed patients, these bacteria can produce meningitis and pneumonia. Methicillin-resistant Staphylococcus aureus (MRSA) has developed resistance to methicillin and other common antibiotics. MRSA is resistant to various drug classes besides penicillin, including fluoroquinolones, tetracyclines, macrolides, and aminoglycosides. This widespread antibiotic resistance makes MRSA a significant public health concern, as it limits treatment options and increases the risk of severe infections [26,27]. E. coli is a Gram-negative Enterobacter host in the human intestinal tract. This Enterobacter commonly causes urinary infections, diarrhea, and foodborne diseases associated with enterotoxin production [12]. P. aeruginosa is an opportunistic Gram-negative facultative aerobic bacterium not part of the human microbiota. Many significant infections are associated with P. aeruginosa as pneumonia, urinary infections, surgical site infections, and bacteremia [28]. Therefore, finding an agent to eradicate these bacteria is essential, so liposomes with different lipid compositions were prepared as carriers of ZnPc to be evaluated against Gram-negative and Gram-positive bacteria.